{"id":245,"date":"2023-12-04T10:23:17","date_gmt":"2023-12-04T15:23:17","guid":{"rendered":"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/chapter\/inflammation-and-fever\/"},"modified":"2023-12-04T10:44:12","modified_gmt":"2023-12-04T15:44:12","slug":"inflammation-and-fever","status":"web-only","type":"chapter","link":"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/chapter\/inflammation-and-fever\/","title":{"raw":"Inflammation and Fever","rendered":"Inflammation and Fever"},"content":{"raw":"\n<div><header><\/header>\n<div>\n<div class=\"textbox textbox--learning-objectives\"><header class=\"textbox__header\">\n<p class=\"textbox__title\">Learning Objectives<\/p>\n\n<\/header>\n<div class=\"textbox__content\">\n\nAt the end of this section, you will be able to:\n<ul>\n \t<li>Identify the signs of inflammation and fever and explain why they occur.<\/li>\n \t<li>Explain the advantages and risks posed by inflammatory responses.<\/li>\n<\/ul>\n<\/div>\n<\/div>\n&nbsp;\n\n<\/div>\n<\/div>\nThe inflammatory response, or [pb_glossary id=\"1044\"]inflammation[\/pb_glossary], is triggered by a cascade of chemical mediators and cellular responses that may occur when cells are damaged and stressed or when pathogens successfully breach the physical barriers of the innate immune system. Although inflammation is typically associated with negative consequences of injury or disease, it is a necessary process insofar as it allows for recruitment of the cellular defenses needed to eliminate pathogens, remove damaged and dead cells, and initiate repair mechanisms. Excessive inflammation, however, can result in local tissue damage and, in severe cases, may even become deadly.\n<h2>Acute Inflammation<\/h2>\nAn early, if not immediate, response to tissue injury is [pb_glossary id=\"1045\"]acute inflammation[\/pb_glossary]. Immediately following an injury, vasoconstriction of blood vessels will occur to minimize blood loss. The amount of [pb_glossary id=\"1037\"]vasoconstriction[\/pb_glossary] is related to the amount of vascular injury, but it is usually brief. Vasoconstriction is followed by [pb_glossary id=\"1038\"]vasodilation[\/pb_glossary] and increased vascular permeability, as a direct result of the release of histamine from resident mast cells. Increased blood flow and vascular permeability can dilute toxins and bacterial products at the site of injury or infection. They also contribute to the five observable signs associated with the inflammatory response: [pb_glossary id=\"1046\"]erythema [\/pb_glossary](redness), [pb_glossary id=\"1047\"]edema[\/pb_glossary], heat, pain, and altered function. Vasodilation and increased vascular permeability are also associated with an influx of phagocytes at the site of injury and\/or infection. This can enhance the inflammatory response because phagocytes may release proinflammatory chemicals when they are activated by cellular distress signals released from damaged cells, by [pb_glossary id=\"1048\"]PAMPs[\/pb_glossary] , or by [pb_glossary id=\"1049\"]opsonins[\/pb_glossary] on the surface of pathogens. Activation of the complement system can further enhance the inflammatory response through the production of the anaphylatoxin C5a. <strong>Figure 5.9<\/strong> illustrates a typical case of acute inflammation at the site of a skin wound.\n\n[caption id=\"\" align=\"aligncenter\" width=\"751\"]<a href=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1094\/2016\/11\/03172553\/OSC_Microbio_17_06_Erythema.jpg\"><img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1094\/2016\/11\/03172553\/OSC_Microbio_17_06_Erythema.jpg\" alt=\"a) a diagram of a wound in the skin that has let pathogens enter. Mast cells release histamines which signal to cells in the blood stream. B) The cells have left the blood stream; these phagocytes are engulfing the pathogens.\" width=\"751\" height=\"346\" data-media-type=\"image\/jpeg\"><\/a> <strong>Figure 5.9<\/strong>&nbsp;<em>(a) Mast cells detect injury to nearby cells and release histamine, initiating an inflammatory response. (b) Histamine increases blood flow to the wound site, and increased vascular permeability allows fluid, proteins, phagocytes, and other immune cells to enter infected tissue. These events result in the swelling and reddening of the injured site, and the increased blood flow to the injured site causes it to feel warm. Inflammation is also associated with pain due to these events stimulating nerve pain receptors in the tissue. The interaction of phagocyte pattern recognition receptors (PRRs) with cellular distress signals and PAMPs and opsonins on the surface of pathogens leads to the release of more proinflammatory chemicals, enhancing the inflammatory response.<\/em>[\/caption]\n\nDuring the period of inflammation, the release of [pb_glossary id=\"1050\"]bradykinin[\/pb_glossary] causes capillaries to remain dilated, flooding tissues with fluids and leading to edema. Increasing numbers of neutrophils are recruited to the area to fight pathogens. As the fight rages on, [pb_glossary id=\"1053\"]pus[\/pb_glossary] forms from the accumulation of neutrophils, dead cells, tissue fluids, and lymph. Typically, after a few days, macrophages will help to clear out this pus. Eventually, tissue repair can begin in the wounded area.\n<h2>Chronic Inflammation<\/h2>\n[caption id=\"attachment_1678\" align=\"alignright\" width=\"399\"]<a href=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1094\/2016\/11\/10193729\/OSC_Microbio_17_06_Granuloma1.jpg\"><img class=\"wp-image-1678\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1094\/2016\/11\/10193729\/OSC_Microbio_17_06_Granuloma1.jpg\" alt=\"A micrograph of a tubercle which consists of many darkly staining cells that form a circular structure.\" width=\"399\" height=\"245\"><\/a> <strong>Figure 5.10<\/strong>. <em>A <strong>tubercle<\/strong> is a granuloma in the lung tissue of a patient with tuberculosis. In this micrograph, white blood cells (stained purple) have walled off a pocket of tissue infected with Mycobacterium tuberculosis. Granulomas also occur in many other forms of disease. (credit: modification of work by Piotrowski WJ, G\u00f3rski P, Duda-Szyma\u0144ska J, Kwiatkowska S)<\/em>[\/caption]\n\nWhen acute inflammation is unable to clear an infectious pathogen, [pb_glossary id=\"1051\"]chronic inflammation[\/pb_glossary] may occur. This often results in an ongoing (and sometimes futile) lower-level battle between the host organism and the pathogen. The wounded area may heal at a superficial level, but pathogens may still be present in deeper tissues, stimulating ongoing inflammation. Additionally, chronic inflammation may be involved in the progression of degenerative neurological diseases such as Alzheimer\u2019s and Parkinson\u2019s, heart disease, and metastatic cancer.\n\nChronic inflammation may lead to the formation of [pb_glossary id=\"1052\"]granulomas[\/pb_glossary], pockets of infected tissue walled off and surrounded by WBCs. Macrophages and other phagocytes wage an unsuccessful battle to eliminate the pathogens and dead cellular materials within a granuloma. One example of a disease that produces chronic inflammation is [pb_glossary id=\"1054\"]tuberculosis[\/pb_glossary], which results in the formation of granulomas in lung tissues. A tubercular granuloma is called a tubercle (Figure 5.10).\n\nChronic inflammation is not just associated with bacterial infections. Chronic inflammation can be an important cause of tissue damage from viral infections. The extensive scarring observed with hepatitis C infections and liver cirrhosis is the result of chronic inflammation.\n<div class=\"textbox shaded\">\n<h3>Chronic Edema<\/h3>\n[caption id=\"\" align=\"alignright\" width=\"400\"]<a href=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1094\/2016\/11\/03172558\/OSC_Microbio_17_06_Elephant.jpg\"><img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1094\/2016\/11\/03172558\/OSC_Microbio_17_06_Elephant.jpg\" alt=\"A photo of a person with extremely swollen lower legs.\" width=\"400\" height=\"391\" data-media-type=\"image\/jpeg\"><\/a> <strong>Figure 5.11<\/strong>&nbsp;<em>Elephantiasis (chronic edema) of the legs due to filariasis. (credit: modification of work by Centers for Disease Control and Prevention)<\/em>[\/caption]\n\nIn addition to granulomas, chronic inflammation can also result in long-term edema. A condition known as[pb_glossary id=\"1055\"] lymphatic filariasis[\/pb_glossary] (also known as elephantiasis) provides an extreme example. Lymphatic filariasis is caused by microscopic nematodes (parasitic worms) whose larvae are transmitted between human hosts by mosquitoes. Adult worms live in the lymphatic vessels, where their presence stimulates infiltration by lymphocytes, plasma cells, eosinophils, and thrombocytes (a condition known as lymphangitis). Because of the chronic nature of the illness, granulomas, fibrosis, and blocking of the lymphatic system may eventually occur. Over time, these blockages may worsen with repeated infections over decades, leading to skin thickened with edema and fibrosis. Lymph (extracellular tissue fluid) may spill out of the lymphatic areas and back into tissues, causing extreme swelling (Figure 5.11). Secondary bacterial infections commonly follow. Because it is a disease caused by a parasite, eosinophilia (a dramatic rise in the number of eosinophils in the blood) is characteristic of acute infection. However, this increase in antiparasite granulocytes is not sufficient to clear the infection in many cases.\n\nLymphatic filariasis affects an estimated 120 million people worldwide, mostly concentrated in Africa and Asia.[footnote]Centers for Disease Control and Prevention. \"Parasites\u2013Lymphatic Filiariasis.\" 2016. http:\/\/www.cdc.gov\/parasites\/lymphaticfilariasis\/gen_info\/faqs.html.[\/footnote] Improved sanitation and mosquito control can reduce transmission rates.\n\n<\/div>\n<h2>Fever<\/h2>\nA [pb_glossary id=\"1056\"]fever[\/pb_glossary] is an inflammatory response that extends beyond the site of infection and affects the entire body, resulting in an overall increase in body temperature. Body temperature is normally regulated and maintained by the hypothalamus, an anatomical section of the brain that functions to maintain homeostasis in the body. However, certain bacterial or viral infections can result in the production of [pb_glossary id=\"1057\"]pyrogens[\/pb_glossary], chemicals that effectively alter the \"thermostat setting\" of the [pb_glossary id=\"1058\"]hypothalamus[\/pb_glossary] to elevate body temperature and cause fever. Pyrogens may be exogenous or endogenous. For example, the endotoxin lipopolysaccharide (LPS), produced by gram-negative bacteria, is an exogenous pyrogen that may induce the leukocytes to release endogenous pyrogens such as interleukin-1 (IL-1), IL-6, interferon-\u03b3 (IFN-\u03b3), and tumour necrosis factor (TNF). In a cascading effect, these molecules can then lead to the release of prostaglandin E2 (PGE<sub>2<\/sub>) from other cells, resetting the hypothalamus to initiate fever (Figure 5.12).\n\n[caption id=\"attachment_1680\" align=\"aligncenter\" width=\"752\"]<a href=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1094\/2016\/11\/10194119\/OSC_Microbio_17_06_Hypothal1-1024x524.jpg\"><img class=\"wp-image-1680\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1094\/2016\/11\/10194119\/OSC_Microbio_17_06_Hypothal1-1024x524.jpg\" alt=\" A diagram with exogenous pyrogen at the top. These activate leukocytes which in turn release IL-6. The leukocytes also produce pyrogenic cytokines (IL-1, TNF-\u03b1, IFN-\u03b3) which lead to the production of IL-6. IL-6 signals the circumventricular organs of the brain to produce PGE2 which results in fever. The temperature dependent feedback on cytokine expression decreases the production of IL-6 in a negative feedback loop.\" width=\"752\" height=\"385\"><\/a> <strong>Figure 5.12<\/strong>&nbsp;<em>The role of the hypothalamus in the inflammatory response. Macrophages recognize pathogens in an area and release cytokines that trigger inflammation. The cytokines also send a signal up the vagus nerve to the hypothalamus.<\/em>[\/caption]\n\nLike other forms of inflammation, a fever enhances the innate immune defenses by stimulating leukocytes to kill pathogens. The rise in body temperature also may inhibit the growth of many pathogens since human pathogens have optimum growth occurring around 35 \u00b0C (95 \u00b0F). In addition, some studies suggest that fever may also stimulate release of iron-sequestering compounds from the liver, thereby starving out microbes that rely on iron for growth.[footnote]N. Parrow et al. \"Sequestration and Scavenging of Iron in Infection.\" <em>Infection and Immunity<\/em> 81 no. 10 (2013):3503\u20133514[\/footnote]\n\nDuring [pb_glossary id=\"1056\"]fever[\/pb_glossary], the skin may appear pale due to [pb_glossary id=\"1037\"]vasoconstriction[\/pb_glossary] of the blood vessels in the skin, which is mediated by the hypothalamus to divert blood flow away from extremities, minimizing the loss of heat and raising the core temperature. The hypothalamus will also stimulate shivering of muscles, another effective mechanism of generating heat and raising the core temperature.\n\nThe crisis phase occurs when the fever breaks. The hypothalamus stimulates [pb_glossary id=\"1038\"]vasodilation[\/pb_glossary], resulting in a return of blood flow to the skin and a subsequent release of heat from the body. The hypothalamus also stimulates sweating, which cools the skin as the sweat evaporates.\n\nAlthough a low-level fever may help an individual overcome an illness, in some instances, this immune response can be too strong, causing tissue and organ damage and, in severe cases, even death. The inflammatory response to bacterial [pb_glossary id=\"1059\"]superantigens[\/pb_glossary] is one scenario in which a life-threatening fever may develop. Superantigens are bacterial or viral proteins that can cause an excessive activation of T cells from the specific adaptive immune defense, as well as an excessive release of cytokines that overstimulates the inflammatory response. For example, <em>Staphylococcus aureus<\/em> and <em>Streptococcus pyogenes<\/em> are capable of producing superantigens that cause toxic shock syndrome and <strong>scarlet fever<\/strong>, respectively. Both of these conditions can be associated with very high, life-threatening fevers in excess of 42 \u00b0C (108 \u00b0F).\n<div>\n<h1>Section Review<\/h1>\n<ul>\n \t<li>Inflammation results from the collective response of chemical mediators and cellular defenses to an injury or infection.<\/li>\n \t<li>Acute inflammation is short lived and localized to the site of injury or infection. Chronic inflammation occurs when the inflammatory response is unsuccessful, and may result in the formation of granulomas (e.g., with tuberculosis) and scarring (e.g., with hepatitis C viral infections and liver cirrhosis).<\/li>\n \t<li>The five cardinal signs of inflammation are erythema, edema, heat, pain, and altered function. These largely result from innate responses that draw increased blood flow to the injured or infected tissue.<\/li>\n \t<li>Fever is a system-wide sign of inflammation that raises the body temperature and stimulates the immune response.<\/li>\n \t<li>Both inflammation and fever can be harmful if the inflammatory response is too severe.<\/li>\n<\/ul>\n<h1>Review Questions<\/h1>\n[h5p id=\"27\"]\n<h1 data-type=\"title\">Adaption<\/h1>\nThis chapter is adapted from the following text:\n\n<a href=\"https:\/\/openstax.org\/books\/microbiology\/pages\/17-5-inflammation-and-fever#0\" target=\"_blank\" rel=\"noopener\">Inflammation and fever<\/a> in <a href=\"https:\/\/openstax.org\/books\/microbiology\/pages\/17-5-inflammation-and-fever?query=%22chronic%20inflammation%22&amp;target=%7B%22type%22%3A%22search%22%2C%22index%22%3A0%7D#fs-id1172100743755\" target=\"_blank\" rel=\"noopener\">Microbiology<\/a> by Rice University (Open Stax) is licensed under a <a href=\"https:\/\/creativecommons.org\/licenses\/by\/4.0\/\">Creative Commons Attribution 4.0 International License<\/a>\n\n<\/div>\n","rendered":"<div>\n<header><\/header>\n<div>\n<div class=\"textbox textbox--learning-objectives\">\n<header class=\"textbox__header\">\n<p class=\"textbox__title\">Learning Objectives<\/p>\n<\/header>\n<div class=\"textbox__content\">\n<p>At the end of this section, you will be able to:<\/p>\n<ul>\n<li>Identify the signs of inflammation and fever and explain why they occur.<\/li>\n<li>Explain the advantages and risks posed by inflammatory responses.<\/li>\n<\/ul>\n<\/div>\n<\/div>\n<p>&nbsp;<\/p>\n<\/div>\n<\/div>\n<p>The inflammatory response, or <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_245_1044\">inflammation<\/a>, is triggered by a cascade of chemical mediators and cellular responses that may occur when cells are damaged and stressed or when pathogens successfully breach the physical barriers of the innate immune system. Although inflammation is typically associated with negative consequences of injury or disease, it is a necessary process insofar as it allows for recruitment of the cellular defenses needed to eliminate pathogens, remove damaged and dead cells, and initiate repair mechanisms. Excessive inflammation, however, can result in local tissue damage and, in severe cases, may even become deadly.<\/p>\n<h2>Acute Inflammation<\/h2>\n<p>An early, if not immediate, response to tissue injury is <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_245_1045\">acute inflammation<\/a>. Immediately following an injury, vasoconstriction of blood vessels will occur to minimize blood loss. The amount of <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_245_1037\">vasoconstriction<\/a> is related to the amount of vascular injury, but it is usually brief. Vasoconstriction is followed by <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_245_1038\">vasodilation<\/a> and increased vascular permeability, as a direct result of the release of histamine from resident mast cells. Increased blood flow and vascular permeability can dilute toxins and bacterial products at the site of injury or infection. They also contribute to the five observable signs associated with the inflammatory response: <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_245_1046\">erythema <\/a>(redness), <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_245_1047\">edema<\/a>, heat, pain, and altered function. Vasodilation and increased vascular permeability are also associated with an influx of phagocytes at the site of injury and\/or infection. This can enhance the inflammatory response because phagocytes may release proinflammatory chemicals when they are activated by cellular distress signals released from damaged cells, by <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_245_1048\">PAMPs<\/a> , or by <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_245_1049\">opsonins<\/a> on the surface of pathogens. Activation of the complement system can further enhance the inflammatory response through the production of the anaphylatoxin C5a. <strong>Figure 5.9<\/strong> illustrates a typical case of acute inflammation at the site of a skin wound.<\/p>\n<figure style=\"width: 751px\" class=\"wp-caption aligncenter\"><a href=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1094\/2016\/11\/03172553\/OSC_Microbio_17_06_Erythema.jpg\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1094\/2016\/11\/03172553\/OSC_Microbio_17_06_Erythema.jpg\" alt=\"a) a diagram of a wound in the skin that has let pathogens enter. Mast cells release histamines which signal to cells in the blood stream. B) The cells have left the blood stream; these phagocytes are engulfing the pathogens.\" width=\"751\" height=\"346\" data-media-type=\"image\/jpeg\" \/><\/a><figcaption class=\"wp-caption-text\"><strong>Figure 5.9<\/strong>&nbsp;<em>(a) Mast cells detect injury to nearby cells and release histamine, initiating an inflammatory response. (b) Histamine increases blood flow to the wound site, and increased vascular permeability allows fluid, proteins, phagocytes, and other immune cells to enter infected tissue. These events result in the swelling and reddening of the injured site, and the increased blood flow to the injured site causes it to feel warm. Inflammation is also associated with pain due to these events stimulating nerve pain receptors in the tissue. The interaction of phagocyte pattern recognition receptors (PRRs) with cellular distress signals and PAMPs and opsonins on the surface of pathogens leads to the release of more proinflammatory chemicals, enhancing the inflammatory response.<\/em><\/figcaption><\/figure>\n<p>During the period of inflammation, the release of <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_245_1050\">bradykinin<\/a> causes capillaries to remain dilated, flooding tissues with fluids and leading to edema. Increasing numbers of neutrophils are recruited to the area to fight pathogens. As the fight rages on, <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_245_1053\">pus<\/a> forms from the accumulation of neutrophils, dead cells, tissue fluids, and lymph. Typically, after a few days, macrophages will help to clear out this pus. Eventually, tissue repair can begin in the wounded area.<\/p>\n<h2>Chronic Inflammation<\/h2>\n<figure id=\"attachment_1678\" aria-describedby=\"caption-attachment-1678\" style=\"width: 399px\" class=\"wp-caption alignright\"><a href=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1094\/2016\/11\/10193729\/OSC_Microbio_17_06_Granuloma1.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-1678\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1094\/2016\/11\/10193729\/OSC_Microbio_17_06_Granuloma1.jpg\" alt=\"A micrograph of a tubercle which consists of many darkly staining cells that form a circular structure.\" width=\"399\" height=\"245\" \/><\/a><figcaption id=\"caption-attachment-1678\" class=\"wp-caption-text\"><strong>Figure 5.10<\/strong>. <em>A <strong>tubercle<\/strong> is a granuloma in the lung tissue of a patient with tuberculosis. In this micrograph, white blood cells (stained purple) have walled off a pocket of tissue infected with Mycobacterium tuberculosis. Granulomas also occur in many other forms of disease. (credit: modification of work by Piotrowski WJ, G\u00f3rski P, Duda-Szyma\u0144ska J, Kwiatkowska S)<\/em><\/figcaption><\/figure>\n<p>When acute inflammation is unable to clear an infectious pathogen, <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_245_1051\">chronic inflammation<\/a> may occur. This often results in an ongoing (and sometimes futile) lower-level battle between the host organism and the pathogen. The wounded area may heal at a superficial level, but pathogens may still be present in deeper tissues, stimulating ongoing inflammation. Additionally, chronic inflammation may be involved in the progression of degenerative neurological diseases such as Alzheimer\u2019s and Parkinson\u2019s, heart disease, and metastatic cancer.<\/p>\n<p>Chronic inflammation may lead to the formation of <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_245_1052\">granulomas<\/a>, pockets of infected tissue walled off and surrounded by WBCs. Macrophages and other phagocytes wage an unsuccessful battle to eliminate the pathogens and dead cellular materials within a granuloma. One example of a disease that produces chronic inflammation is <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_245_1054\">tuberculosis<\/a>, which results in the formation of granulomas in lung tissues. A tubercular granuloma is called a tubercle (Figure 5.10).<\/p>\n<p>Chronic inflammation is not just associated with bacterial infections. Chronic inflammation can be an important cause of tissue damage from viral infections. The extensive scarring observed with hepatitis C infections and liver cirrhosis is the result of chronic inflammation.<\/p>\n<div class=\"textbox shaded\">\n<h3>Chronic Edema<\/h3>\n<figure style=\"width: 400px\" class=\"wp-caption alignright\"><a href=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1094\/2016\/11\/03172558\/OSC_Microbio_17_06_Elephant.jpg\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1094\/2016\/11\/03172558\/OSC_Microbio_17_06_Elephant.jpg\" alt=\"A photo of a person with extremely swollen lower legs.\" width=\"400\" height=\"391\" data-media-type=\"image\/jpeg\" \/><\/a><figcaption class=\"wp-caption-text\"><strong>Figure 5.11<\/strong>&nbsp;<em>Elephantiasis (chronic edema) of the legs due to filariasis. (credit: modification of work by Centers for Disease Control and Prevention)<\/em><\/figcaption><\/figure>\n<p>In addition to granulomas, chronic inflammation can also result in long-term edema. A condition known as<a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_245_1055\"> lymphatic filariasis<\/a> (also known as elephantiasis) provides an extreme example. Lymphatic filariasis is caused by microscopic nematodes (parasitic worms) whose larvae are transmitted between human hosts by mosquitoes. Adult worms live in the lymphatic vessels, where their presence stimulates infiltration by lymphocytes, plasma cells, eosinophils, and thrombocytes (a condition known as lymphangitis). Because of the chronic nature of the illness, granulomas, fibrosis, and blocking of the lymphatic system may eventually occur. Over time, these blockages may worsen with repeated infections over decades, leading to skin thickened with edema and fibrosis. Lymph (extracellular tissue fluid) may spill out of the lymphatic areas and back into tissues, causing extreme swelling (Figure 5.11). Secondary bacterial infections commonly follow. Because it is a disease caused by a parasite, eosinophilia (a dramatic rise in the number of eosinophils in the blood) is characteristic of acute infection. However, this increase in antiparasite granulocytes is not sufficient to clear the infection in many cases.<\/p>\n<p>Lymphatic filariasis affects an estimated 120 million people worldwide, mostly concentrated in Africa and Asia.<a class=\"footnote\" title=\"Centers for Disease Control and Prevention. &quot;Parasites\u2013Lymphatic Filiariasis.&quot; 2016. http:\/\/www.cdc.gov\/parasites\/lymphaticfilariasis\/gen_info\/faqs.html.\" id=\"return-footnote-245-1\" href=\"#footnote-245-1\" aria-label=\"Footnote 1\"><sup class=\"footnote\">[1]<\/sup><\/a> Improved sanitation and mosquito control can reduce transmission rates.<\/p>\n<\/div>\n<h2>Fever<\/h2>\n<p>A <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_245_1056\">fever<\/a> is an inflammatory response that extends beyond the site of infection and affects the entire body, resulting in an overall increase in body temperature. Body temperature is normally regulated and maintained by the hypothalamus, an anatomical section of the brain that functions to maintain homeostasis in the body. However, certain bacterial or viral infections can result in the production of <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_245_1057\">pyrogens<\/a>, chemicals that effectively alter the &#8220;thermostat setting&#8221; of the <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_245_1058\">hypothalamus<\/a> to elevate body temperature and cause fever. Pyrogens may be exogenous or endogenous. For example, the endotoxin lipopolysaccharide (LPS), produced by gram-negative bacteria, is an exogenous pyrogen that may induce the leukocytes to release endogenous pyrogens such as interleukin-1 (IL-1), IL-6, interferon-\u03b3 (IFN-\u03b3), and tumour necrosis factor (TNF). In a cascading effect, these molecules can then lead to the release of prostaglandin E2 (PGE<sub>2<\/sub>) from other cells, resetting the hypothalamus to initiate fever (Figure 5.12).<\/p>\n<figure id=\"attachment_1680\" aria-describedby=\"caption-attachment-1680\" style=\"width: 752px\" class=\"wp-caption aligncenter\"><a href=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1094\/2016\/11\/10194119\/OSC_Microbio_17_06_Hypothal1-1024x524.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-1680\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1094\/2016\/11\/10194119\/OSC_Microbio_17_06_Hypothal1-1024x524.jpg\" alt=\"A diagram with exogenous pyrogen at the top. These activate leukocytes which in turn release IL-6. The leukocytes also produce pyrogenic cytokines (IL-1, TNF-\u03b1, IFN-\u03b3) which lead to the production of IL-6. IL-6 signals the circumventricular organs of the brain to produce PGE2 which results in fever. The temperature dependent feedback on cytokine expression decreases the production of IL-6 in a negative feedback loop.\" width=\"752\" height=\"385\" \/><\/a><figcaption id=\"caption-attachment-1680\" class=\"wp-caption-text\"><strong>Figure 5.12<\/strong>&nbsp;<em>The role of the hypothalamus in the inflammatory response. Macrophages recognize pathogens in an area and release cytokines that trigger inflammation. The cytokines also send a signal up the vagus nerve to the hypothalamus.<\/em><\/figcaption><\/figure>\n<p>Like other forms of inflammation, a fever enhances the innate immune defenses by stimulating leukocytes to kill pathogens. The rise in body temperature also may inhibit the growth of many pathogens since human pathogens have optimum growth occurring around 35 \u00b0C (95 \u00b0F). In addition, some studies suggest that fever may also stimulate release of iron-sequestering compounds from the liver, thereby starving out microbes that rely on iron for growth.<a class=\"footnote\" title=\"N. Parrow et al. &quot;Sequestration and Scavenging of Iron in Infection.&quot; Infection and Immunity 81 no. 10 (2013):3503\u20133514\" id=\"return-footnote-245-2\" href=\"#footnote-245-2\" aria-label=\"Footnote 2\"><sup class=\"footnote\">[2]<\/sup><\/a><\/p>\n<p>During <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_245_1056\">fever<\/a>, the skin may appear pale due to <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_245_1037\">vasoconstriction<\/a> of the blood vessels in the skin, which is mediated by the hypothalamus to divert blood flow away from extremities, minimizing the loss of heat and raising the core temperature. The hypothalamus will also stimulate shivering of muscles, another effective mechanism of generating heat and raising the core temperature.<\/p>\n<p>The crisis phase occurs when the fever breaks. The hypothalamus stimulates <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_245_1038\">vasodilation<\/a>, resulting in a return of blood flow to the skin and a subsequent release of heat from the body. The hypothalamus also stimulates sweating, which cools the skin as the sweat evaporates.<\/p>\n<p>Although a low-level fever may help an individual overcome an illness, in some instances, this immune response can be too strong, causing tissue and organ damage and, in severe cases, even death. The inflammatory response to bacterial <a class=\"glossary-term\" aria-haspopup=\"dialog\" aria-describedby=\"definition\" href=\"#term_245_1059\">superantigens<\/a> is one scenario in which a life-threatening fever may develop. Superantigens are bacterial or viral proteins that can cause an excessive activation of T cells from the specific adaptive immune defense, as well as an excessive release of cytokines that overstimulates the inflammatory response. For example, <em>Staphylococcus aureus<\/em> and <em>Streptococcus pyogenes<\/em> are capable of producing superantigens that cause toxic shock syndrome and <strong>scarlet fever<\/strong>, respectively. Both of these conditions can be associated with very high, life-threatening fevers in excess of 42 \u00b0C (108 \u00b0F).<\/p>\n<div>\n<h1>Section Review<\/h1>\n<ul>\n<li>Inflammation results from the collective response of chemical mediators and cellular defenses to an injury or infection.<\/li>\n<li>Acute inflammation is short lived and localized to the site of injury or infection. Chronic inflammation occurs when the inflammatory response is unsuccessful, and may result in the formation of granulomas (e.g., with tuberculosis) and scarring (e.g., with hepatitis C viral infections and liver cirrhosis).<\/li>\n<li>The five cardinal signs of inflammation are erythema, edema, heat, pain, and altered function. These largely result from innate responses that draw increased blood flow to the injured or infected tissue.<\/li>\n<li>Fever is a system-wide sign of inflammation that raises the body temperature and stimulates the immune response.<\/li>\n<li>Both inflammation and fever can be harmful if the inflammatory response is too severe.<\/li>\n<\/ul>\n<h1>Review Questions<\/h1>\n<h1 data-type=\"title\">Adaption<\/h1>\n<p>This chapter is adapted from the following text:<\/p>\n<p><a href=\"https:\/\/openstax.org\/books\/microbiology\/pages\/17-5-inflammation-and-fever#0\" target=\"_blank\" rel=\"noopener\">Inflammation and fever<\/a> in <a href=\"https:\/\/openstax.org\/books\/microbiology\/pages\/17-5-inflammation-and-fever?query=%22chronic%20inflammation%22&amp;target=%7B%22type%22%3A%22search%22%2C%22index%22%3A0%7D#fs-id1172100743755\" target=\"_blank\" rel=\"noopener\">Microbiology<\/a> by Rice University (Open Stax) is licensed under a <a href=\"https:\/\/creativecommons.org\/licenses\/by\/4.0\/\">Creative Commons Attribution 4.0 International License<\/a><\/p>\n<\/div>\n<hr class=\"before-footnotes clear\" \/><div class=\"footnotes\"><ol><li id=\"footnote-245-1\">Centers for Disease Control and Prevention. \"Parasites\u2013Lymphatic Filiariasis.\" 2016. http:\/\/www.cdc.gov\/parasites\/lymphaticfilariasis\/gen_info\/faqs.html. <a href=\"#return-footnote-245-1\" class=\"return-footnote\" aria-label=\"Return to footnote 1\">&crarr;<\/a><\/li><li id=\"footnote-245-2\">N. Parrow et al. \"Sequestration and Scavenging of Iron in Infection.\" <em>Infection and Immunity<\/em> 81 no. 10 (2013):3503\u20133514 <a href=\"#return-footnote-245-2\" class=\"return-footnote\" aria-label=\"Return to footnote 2\">&crarr;<\/a><\/li><\/ol><\/div><div class=\"glossary\"><span class=\"screen-reader-text\" id=\"definition\">definition<\/span><template id=\"term_245_1044\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_245_1044\"><div tabindex=\"-1\"><p>a necessary process that recruits the cellular defenses needed to eliminate pathogens, remove damaged and dead cells, and initiate repair mechanisms<\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_245_1045\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_245_1045\"><div tabindex=\"-1\"><p>inflammatory response that occurs from the time of injury to infection up to a few days<\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_245_1037\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_245_1037\"><div tabindex=\"-1\"><p>constriction of the smooth muscle of a blood vessel, resulting in a decreased vascular diameter<\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_245_1038\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_245_1038\"><div tabindex=\"-1\"><p>relaxation of the smooth muscle in the wall of a blood vessel, resulting in an increased vascular diameter<\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_245_1046\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_245_1046\"><div tabindex=\"-1\"><p>increased blood in tissue, resulting in visible redness and increased heat <\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_245_1047\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_245_1047\"><div tabindex=\"-1\"><p>'swelling' of tissue, most often due to increased fluid in the interstitial spaces<\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_245_1048\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_245_1048\"><div tabindex=\"-1\"><p>Pathogen-associated molecular patterns are small molecular motifs conserved within a class of microbes.<\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_245_1049\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_245_1049\"><div tabindex=\"-1\"><p>extracellular proteins that mark it to be be phagocytosed <\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_245_1050\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_245_1050\"><div tabindex=\"-1\"><p>a pro-inflammatory peptide with many vasoactive and inflammatory effects  <\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_245_1053\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_245_1053\"><div tabindex=\"-1\"><p>a protein-rich fluid formed at the site of inflammation during bacterial or fungal infection. Filled with dead cells and leukocytes, pus is typically white-yellow, yellow, or yellow-brown.<\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_245_1051\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_245_1051\"><div tabindex=\"-1\"><p>a slow, long-term inflammation, in response to repeated injury, lasting for weeks, months to years.<\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_245_1052\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_245_1052\"><div tabindex=\"-1\"><p>pockets of infected tissue walled off and surrounded by white blood cells<\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_245_1054\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_245_1054\"><div tabindex=\"-1\"><p>an infectious bacterial disease (usually caused by Mycobacterium tuberculosis  bacteria) that generally affects the lungs, but can also affect other parts of the body<\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_245_1055\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_245_1055\"><div tabindex=\"-1\"><p>parasitic worms that live in the lymphatic vessels causing a chronic  inflammatory response. This results in   blockage of lymph flow causing edema, repeated infections, skin thickening and fibrosis. <\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_245_1056\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_245_1056\"><div tabindex=\"-1\"><p>a systemic inflammatory response that extends beyond the site of infection and affects the entire body, resulting in an overall increase in body temperature<\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_245_1057\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_245_1057\"><div tabindex=\"-1\"><p>chemicals that effect the temperature set point in the  hypothalamus, thus elevating body temperature and causing fever.<\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_245_1058\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_245_1058\"><div tabindex=\"-1\"><p>part of the brain below the thalamus that is an important interface between the central nervous system and vasculature. Amongst its many functions, it plays a major role in hormonal secretion, temperature and fluid homeostasis, and emotional regulation.<\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><template id=\"term_245_1059\"><div class=\"glossary__definition\" role=\"dialog\" data-id=\"term_245_1059\"><div tabindex=\"-1\"><p>bacterial or viral proteins that can cause an excessive inflammatory response <\/p>\n<\/div><button><span aria-hidden=\"true\">&times;<\/span><span class=\"screen-reader-text\">Close definition<\/span><\/button><\/div><\/template><\/div>","protected":false},"author":103,"menu_order":12,"template":"","meta":{"pb_show_title":"on","pb_short_title":"","pb_subtitle":"","pb_authors":["nina-parker","mark-schneegurt","anh-hue-thi-tu","philip-lister","brian-m-forster"],"pb_section_license":"cc-by"},"chapter-type":[],"contributor":[79],"license":[53],"class_list":["post-245","chapter","type-chapter","status-web-only","hentry","contributor-brian-m-forster","license-cc-by"],"part":205,"_links":{"self":[{"href":"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/wp-json\/pressbooks\/v2\/chapters\/245","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/wp-json\/pressbooks\/v2\/chapters"}],"about":[{"href":"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/wp-json\/wp\/v2\/types\/chapter"}],"author":[{"embeddable":true,"href":"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/wp-json\/wp\/v2\/users\/103"}],"version-history":[{"count":1,"href":"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/wp-json\/pressbooks\/v2\/chapters\/245\/revisions"}],"predecessor-version":[{"id":1259,"href":"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/wp-json\/pressbooks\/v2\/chapters\/245\/revisions\/1259"}],"part":[{"href":"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/wp-json\/pressbooks\/v2\/parts\/205"}],"metadata":[{"href":"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/wp-json\/pressbooks\/v2\/chapters\/245\/metadata\/"}],"wp:attachment":[{"href":"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/wp-json\/wp\/v2\/media?parent=245"}],"wp:term":[{"taxonomy":"chapter-type","embeddable":true,"href":"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/wp-json\/pressbooks\/v2\/chapter-type?post=245"},{"taxonomy":"contributor","embeddable":true,"href":"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/wp-json\/wp\/v2\/contributor?post=245"},{"taxonomy":"license","embeddable":true,"href":"https:\/\/pressbooks.bccampus.ca\/dcbiol2200\/wp-json\/wp\/v2\/license?post=245"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}