Inflammation (Latin, inflammatio, to set on fire) is the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. Inflammation is not a synonym for infection. Even in cases where inflammation is caused by infection it is incorrect to use the terms as synonyms: infection is caused by an exogenous pathogen, while inflammation is the response of the organism to the pathogen.
In the absence of inflammation, wounds and infections would never heal and progressive destruction of the tissue would compromise the survival of the organism. However, inflammation which runs unchecked can also lead to a host of diseases, such as hay fever, atherosclerosis, and rheumatoid arthritis. It is for this reason that inflammation is normally tightly regulated by the body.
Inflammation can be classified as either acute or chronic. Acute inflammation is the initial response of the body to harmful stimuli and is achieved by the increased movement of plasma and leukocytes from the blood into the injured tissues. A cascade of biochemical events propagates and matures the inflammatory response, involving the local vascular system, the immune system, and various cells within the injured tissue. Prolonged inflammation, known as chronic inflammation, leads to a progressive shift in the type of cells which are present at the site of inflammation and is characterised by simultaneous destruction and healing of the tissue from the inflammatory process.
|Loss of function||Functio laesa|
Acute inflammation is a short term process which is characterised by the classic signs of inflammation - swelling, redness, pain, heat, and loss of function - due to the infiltration of the tissues by plasma and leukocytes. It occurs as long as the injurious stimuli is present and ceases once the stimuli has been removed, broken down, or walled off by scarring (fibrosis). The first four characteristics have been known since ancient times and are attributed to Celsus. Loss of function was added to the definition of inflammation by Rudolf Virchow in the 19th century.
The process of acute inflammation is initiated by the blood vessels local to the injured tissue, which alter to allow the exudation of plasma proteins and leukocytes into the surrounding tissue. The increased flow of fluid into the tissue causes the characteristic swelling associated with inflammation, and the increased blood flow to the area causes the reddened colour and increased heat. The blood vessels also alter to permit the extravasation of leukocytes through the endothelium and basement membrane constituting the blood vessel. Once in the tissue, the cells migrate along a chemotactic gradient to reach the site of injury, where they can attempt to remove the stimulus and repair the tissue.
Meanwhile, several biochemical cascade systems, consisting of chemicals known as plasma-derived inflammatory mediators, act in parallel to propagate and mature the inflammatory response. These include the complement system, coagulation system and fibrinolysis system.
Finally, down-regulation of the inflammatory response concludes acute inflammation. Removal of the injurious stimuli halts the response of the inflammatory mechanisms, which require constant stimulation to propagate the process. Additionally, many inflammatory mediators have short half lives and are quickly degraded in the tissue, helping to quickly cease the inflammatory response once the stimulus has been removed.
Chronic inflammation is a pathological condition characterised by concurrent active inflammation, tissue destruction, and attempts at repair. Chronic inflammation is not characterised by the classic signs of acute inflammation listed above. Instead, chronically inflamed tissue is characterised by the infiltration of mononuclear immune cells (monocytes, macrophages, lymphocytes, and plasma cells), tissue destruction, and attempts at healing, which include angiogenesis and fibrosis.
The exudative component involves the movement of plasma fluid, containing important proteins such as fibrin and immunoglobulins (antibodies), into inflamed tissue. This movement is achieved via the chemically-induced dilation and increased permeability of blood vessels, which results in a net loss of blood plasma. The increased collection of fluid into the tissue causes it to swell (edema).
Acute inflammation is characterised by marked vascular changes, including vasodilation, increased permeability, and the slowing of blood flow, which are induced by the actions of various inflammatory mediators. Vasodilation occurs first at the arteriole level, progressing to the capillary level, and brings about a net increase in the amount of blood present, causing the redness and heat of inflammation. Increased permeability of the vessels results in the movement of plasma into the tissues, with resultant stasis due to the increase in the concentration of the cells within blood - a condition characterised by enlarged vessels packed with cells. Stasis allows leukocytes to marginate along the endothelium, a process critical to their recruitment into the tissues. Normal flowing blood prevents this, as the shearing force along the periphery of the vessels moves cells in the blood into the middle of the vessel.
|Bradykinin||Kinin system||A vasoactive protein which is able to induce vasodilation, increase vascular permeability, cause smooth muscle contraction, and induce pain.|
|C3||Complement system||Cleaves to produce C3a and C3b. C3a stimulates histamine release by mast cells, thereby producing vasodilation. C3b is able to bind to bacterial cell walls and act as an opsonin, which marks the invader as a target for phagocytosis.|
|C5a||Complement system||Stimulates histamine release by mast cells, thereby producing vasodilation. It is also able to act as a chemoattractant to direct cells via chemotaxis to the site of inflammation.|
|Factor XII||Liver||A protein which circulates inactively, until activated by collagen, platelets, or exposed basement membranes via conformational change. When activated, it in turn is able to activate the four plasma systems involved in inflammation: the complement system, kinin system, fibrinolysis system, and coagulation system.|
|Membrane attack complex||Complement system||A complex of the complement proteins C5b, C6, C7, C8, and multiple units of C9. The combination and activation of this range of complement proteins forms the membrane attack complex, which is able to insert into bacterial cell walls and causes cell lysis with ensuing death.|
|Plasmin||Fibrinolysis system||Able to break down fibrin clots, cleave complement protein C3, and activate Factor XII.|
|Thrombin||Coagulation system||Cleaves the soluble plasma protein fibrinogen to produce insoluable fibrin, which aggregates to form a blood clot. Thrombin can also bind to cells via the PAR1 receptor to trigger several other inflammatory responses, such as production of chemokines and nitric oxide.|
The cellular component involves leukocytes, which normally reside in blood and must move into the inflamed tissue via extravasation to aid in inflammation. Some act as phagocytes, ingesting bacteria, viruses, and cellular debris. Others release enzymatic granules which damage pathogenic invaders. Leukocytes also release inflammatory mediators which develop and maintain the inflammatory response. Generally speaking, acute inflammation is mediated by granulocytes, while chronic inflammation is mediated by mononuclear cells such as monocytes and lymphocytes.
Various leukocytes are critically involved in the initiation and maintenance of inflammation. These cells must be able to get to the site of injury from their usual location in the blood, therefore mechanisms exist to recruit and direct leukocytes to the appropriate place. The process of leukocyte movement from the blood to the tissues through the blood vessels is known as extravasation, and can be divided up into a number of broad steps:
|Lysosome granules||Enzymes||Granulocytes||These cells contain a large variety of enzymes which perform a number of functions. Granules can be classified as either specific or azurophilic depending upon the contents, and are able to break down a number of substances, some of which may be plasma-derived proteins which allow these enzymes to act as inflammatory mediators.|
|Histamine||Vasoactive amine||Mast cells, basophils, platelets||Stored in preformed granules, histamine is released in response to a number of stimuli. It causes arteriole dilation and increased venous permeability.|
|IL-8||Chemokine||Primarily macrophages||Activation and chemoattraction of neutrophils, with a weak effect on monocytes and eosinophils.|
|Leukotriene B4||Eicosanoid||Leukocytes||Able to mediate leukocyte adhesion and activation, allowing them to bind to the endothelium and migrate across it. In neutrophils, it is also a potent chemoattractant, and is able to induce the formation of reactive oxygen species and the release of lysosome enzymes by these cells.|
|Nitric oxide||Soluble gas||Macrophages, endothelial cells, some neurons||Potent vasodilator, relaxes smooth muscle, reduces platelet aggregation, aids in leukocyte recruitment, direct antimicrobial activity in high concentrations.|
|Prostaglandins||Eicosanoid||Mast cells||A group of proteins which can cause vasodilation, fever, and pain.|
|TNF and IL-1||Cytokine||Primarily macrophages||Both affect a wide variety of cells to induce many inflammatory reactions: fever, production of cytokines, endothelial gene regulation, chemotaxis, leukocyte adherence, activation of fibroblasts. Responsible for the systemic effects of inflammation, such as loss of appetite and increased heart rate.|
Specific patterns of acute and chronic inflammation are seen during particular situations that arise in the body, such as when inflammation occurs on an epithelial surface, or pyogenic bacteria are involved.
When inflammation overwhelms the whole organism, systemic inflammatory response syndrome is diagnosed. When it is due to infection, the term sepsis is applied. Vasodilation and organ dysfunction are serious problems that may lead to septic shock and death. Inflammation often affects the numbers of leukocytes present in the body:
With the discovery of interleukins, the concept of systemic inflammation developed. Although the processes involved are identical to tissue inflammation, systemic inflammation is not confined to a particular tissue but involves the endothelium and other organ systems. High levels of several inflammation-related markers such as IL-6, IL-8, and TNF-α are associated with obesity. During clinical studies, inflammatory-related molecule levels were reduced and increased levels of anti-inflammatory molecules were seen within four weeks after patients began a very low calorie diet. The association of systemic inflammation with insulin resistance and atherosclerosis is the subject of intense research.
Inflammation also induces high levels of acute-phase proteins, which include C-reactive protein, serum amyloid A, serum amyloid P, vasopressin, and glucocorticoids, which all have varying effects on the body. In acute inflammation, these proteins prove beneficial, however in chronic inflammation they can cause amyloidosis.
Other systemic effects include:
The outcome in a particular circumstance will be determined by the tissue in which the injury has occurred and the injurious agent that is causing it. There are three possible outcomes to inflammation:
Inflammation is usually indicated by adding the suffix "-itis", as shown below. However, some conditions such as asthma and pneumonia do not follow this convention. More examples are available at list of types of inflammation.
|Disease | Necrosis | Infection | Ischemia | Inflammation | Wound healing | Neoplasia|
Surgical pathology |
Molecular pathology |
Forensic Pathology |
Gross examination | Histopathology | Immunohistochemistry | Electron microscopy | Immunofluorescence | Fluorescent in situ hybridization
Clinical chemistry |
Transfusion medicine |
Medical microbiology |
Enzyme assay | Mass spectrometry | Chromatography | Flow cytometry | Blood bank | Microbiological culture | Serology
The content of this section is licensed under the GNU Free Documentation License (local copy). It uses material from the Wikipedia article "Inflammation" modified May 22, 2007 with previous authors listed in its history.