It is characterized by coexisting inflammation, tissue injury, attempted repair by scarring, and immune response.
The cellular infiltrate consists of macrophages, lymphocytes, plasma cells, and other leukocytes.
It is mediated by cytokines produced by macrophages and lymphocytes (notably T lymphocytes); bidirectional interactions between these cells tend to amplify and prolong the inflammatory reaction.
Granulomatous inflammation is a morphologically specific pattern of chronic inflammation induced by T cell and macrophage activation in response to an agent that is resistant to eradication.
Inflammation, even if it is localized, is associated with cytokine-induced systemic reactions that are collectively called the acute-phase response. Anyone who has suffered through a severe bout of a bacterial or viral illness (e.g., pneumonia or influenza) has experienced the systemic manifestations of acute inflammation. These changes are reactions to cytokines whose production is stimulated by bacterial products such as LPS, viral double stranded RNA and by other inflammatory stimuli. The cytokines TNF, IL-1, and IL-6 are important mediators of the acute-phase reaction; other cytokines, notably type I interferons, also contribute to the reaction.
The acute-phase response consists of several clinical and pathologic changes:
Fever, characterized by an elevation of body temperature, usually by 1° to 4°C, is one of the most prominent manifestations of the acute-phase response, especially when inflammation is associated with infection. Substances that induce fever are called pyrogens. The increase in body temperature is caused by prostaglandins that are produced in the vascular and perivascular cells of the hypothalamus. Bacterial products, such as LPS (called exogenous pyrogens), stimulate leukocytes to release cytokines such as IL-1 and TNF (called endogenous pyrogens) that increase the enzymes (cyclooxygenases) that convert arachadonic acid into prostaglandins. In the hypothalamus, the prostaglandins, especially PGE2, stimulate the production of neurotransmitters that reset the temperature set point at a higher level. NSAIDs, including aspirin, reduce fever by inhibiting prostaglandin synthesis. How, and even if, fever contributes to the protective host response remains unclear.
Acute-phase proteins are plasma proteins, mostly synthesized in the liver, whose plasma concentrations may increase several hundred-fold as part of the response to inflammatory stimuli. Three of the best-known of these proteins are C-reactive protein (CRP), fibrinogen, and serum amyloid A (SAA) protein. Synthesis of these molecules in hepatocytes is stimulated by cytokines. Many acute-phase proteins, such as CRP and SAA, bind to microbial cell walls, and they may act as opsonins and fix complement. Fibrinogen binds to red cells and causes them to form stacks (rouleaux) that sediment more rapidly at unit gravity than do individual red cells. This is the basis for measuring the erythrocyte sedimentation rate as a simple test for an inflammatory response caused by any stimulus. Acute-phase proteins have beneficial effects during acute inflammation, but prolonged production of these proteins (especially SAA) in states of chronic inflammation can, in some cases, cause secondary amyloidosis (Chapter 5). Elevated serum levels of CRP serve as a marker for increased risk of myocardial infarction in patients with coronary artery disease. It is postulated that inflammation involving atherosclerotic plaques in the coronary arteries predisposes to http://ebooksmedicine.net thrombosis and subsequent infarction. Another peptide whose production is increased in the acute-phase response is the iron-regulating peptide hepcidin. Chronically elevated plasma concentrations of hepcidin reduce the availability of iron and are responsible for the anemia associated with chronic inflammation (Chapter 12).