Inflammatory response cytokines

In the very early phases of the acute inflammatory response most of the cells invading the damaged area are polymorphonuclear neutrophils, also denoted as PMNs, which serve as initial line of defense and source of proinflammatory cytokines. These cells, which usually live for 4-5 days, circulate in the blood until they are attracted by chemokines into injured tissues. Whereas physical injury does not recruit many neutrophils, infections with bacteria or fungi elicit a striking neutrophil response. The characteristic pus of a bacterial abscess is composed mainly of apoptotic (apoptosis) and necrotic PMNs. Emigration of neutrophils from the blood starts with a process denoted as margination where neutrophils come to lie at the periphery of flowing blood cells and adhere to endothelial cells (Fig. 1). L-Selectin is expressed... 

Melanocortin peptides are potent anti-inflammatory agents displaying beneficial effects in diseases ranging from cardiovascular to arthritis to obesity to name a few. Within an inflammatory context, they have the ability to switch off early production of cytokines and at later stages they increase levels of anti-inflammatory proteins that lead to the resolution of the host inflammatory response potentially restoring homeostasis to the tissue. They could eventually be viewed as an alternative to glucocorticoids, as their mode of action often resembles that seen... 

TNF. Tumor necrosis factor. TNFs are among the important cytokines playing a key role in activation and induction of some immune system cells and cellular immunity processes responsible for proinflammatory and inflammatory response reactions as well. 

When looking at macrophage function in mediating inflammatory responses, several groups have shown either a marked induction or suppression of cytokine and... 

Arai K., Lee E, Miyajima A., Miyatake S., Arai N. Yokota T. (1990) Cytokines coordinators of immune and inflammatory responses. Ann Rev5ioc/2em, 59, 783-836. 

The inflammatory response in UC is propagated by atypical type 2 helper T cells that produce proinflammatory cytokines such as interleukin-1 (IL-1), IL-6, and tumor necrosis factor (TNF).7 As discussed previously, a genetic predisposition to UC may partially explain the development of excessive colonic and rectal inflammation. The finding of positive perinuclear antineutrophil cytoplasmic antibodies (pANCA) in association with the human leukocyte antigen (HLA)-DR2 allele in a large percentage of patients with UC supports this theory.4,12... 

Corticosteroids have various effects on immune and inflammatory response systems, although their exact mechanism of immunosuppression is not fully understood. It is generally believed that at high doses, the agents are directly lymphotoxic, and at lower doses, the corticosteroids act by inhibiting the production of various cytokines that are necessary to amplify the immune response.11... 

The adjunctive agent dexamethasone has been shown to improve outcomes in selected patient populations with meningitis. Dexamethasone inhibits the release of proinflammatory cytokines and limits the CNS inflammatory response stimulated by infection and antibiotic therapy. 

Fig. 11.1. Atherogenesis is a persistent inflammatory response that occurs in response to conditions that cause endothelial damage (e.g., hypercholesterolemia and oxLDL). After endothelial cells are activated, they elaborate cytokines, chemokines, and other mediators that recruit mononuclear cells (monocytes and T lymphocytes) to extravasate into the vessel wall where they are activated and release additional proinflammatory factors. Macrophages are able to take up oxLDL via scavenger receptors causing them to differentiate into foam cells and form a fatty streak that progresses to an atheroma with a necrotic lipid core and a fibrous cap. Chemokines can lead to weakening of the fibrous cap and eventual plaque rupture leading to thrombosis and occlusion of the involved vessel.

Fig. 14.1. The Thl/Th2 balance is central to the regulation of normal wound repair. Tissue injury results in the initiation of an inflammatory response, mediated by a variety of cells and their by-products. Immune cells are recruited and cross-regulate the Thl/ Th2 balance that occurs in response to the cytokine environment. This balance is in turn cross-regulated by the chemokine/chemokine-receptor expression profile, which functions to amplify the inflammatory process. Cells residing in the injured tissue release profibrotic mediators, which promote fibroblast activation, proliferation, and differentiation to the myofibroblast phenotype. Myofibroblasts produce collagen to repair damaged tissue, which is an event that is favored by the inhibition of MMP activity. The Thl/Th2 balance is central to whether a normal or aberrant wound-repair process is established A Thl environment promotes normal tissue resolution (fibrinolysis), whereas a Th2 environment maintains the progression of fibrotic disease (excessive collagen deposition).

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