Immune and Defense Mechanisms

The inflammatory response is a highly complex process that involves a number of cell types of the reticuloen-dothelial system and a number of chemical mediators, including prostaglandins, leukotrienes, kinins, and bio-genic amines (See Chapter 36).The inhibitory effects of glucocorticoids on various aspects of the inflammatory and immunological responses constitute the basis for their therapeutic efficacy. All steps of the inflammatory process are blocked: there is a diminution in heat, erythema, swelling, and tenderness. Both the early components (edema, fibrin deposition, neutrophil migration, and phagocytosis) and late components (collagen synthesis and deposition) may be retarded.

Glucocorticoids promote apoptosis and reduce survival, differentiation, and proliferation of a variety of inflammatory cells, including T lymphocytes and macrophages. These effects are mediated by changes in the production and activity of inflammatory cytokines, such as interleukin (IL) 6 and IL-p, tumor necrosis factor-a, and interferon-y. Many of the antiinflammatory actions of glucocorticoids are mediated by cross-talk between the activated glucocorticoid receptor and transcription factors, such as the proinflammatory nuclear factor-K-B (NF-kB) and activator protein (AP) 1. These transcription factors, which promote the expression of a number of inflammatory genes, are potential targets for antiinflammatory therapy as observed in asthma, for example.

A prominent histological feature of glucocorticoid action on the late-phase response to bronchial inhalation challenge with antigen is inhibition of the influx of polymorphonuclear leukocytes, eosinophils, basophils, mononuclear cells, and lymphocytes into tissues (Fig. 60.2). The ability of glucocorticoids to alter reticuloendothelial cell traffic, which is a prominent antiinflamma-tory action of glucocorticoids, is regulated by adhesion molecules. Glucocorticoids reduce the expression of adhesion molecules through the inhibition of proinflam-

matory cytokines and by direct inhibitory effects on the expression of adhesion molecules. Chemotactic cytokines, such as IL-8, which attract immune cells to the inflammatory site, are also inhibited by glucocorticoids. In addition to their ability to inhibit the adherence of inflammatory cells, particularly neutrophils, to the vascular endothelium, steroids are vasoconstrictors. This action would further impede inflammatory cell migration into tissues.

As mentioned previously, glucocorticoids promote apoptosis and reduce survival, differentiation, and proliferation of a number of inflammatory cells. While there is an increase in the number of polymorphonu-clear leukocytes in the circulation, corticosteroids cause the involution and atrophy of all lymphoid tissue and decrease the number of circulating lymphocytes. The striking lymphocytopenia is caused in large part by an inhibition of lymphocyte proliferation, although diminished growth with preferential accumulation of cells in the Gj-phase of the cell cycle is followed by cell death. These effects are mainly mediated by alterations in cy-tokine production and action.

Another important aspect of the inflammatory cascade is arachidonic acid metabolism, leading to the synthesis of the proinflammatory prostaglandins and leukotrienes. Through the formation of lipocortin, an inhibitor of phospholipase A2, glucocorticoids depress the release of arachidonic acid from phospholipids and hence the production of arachidonic acid metabolites.

How To Deal With Rosacea and Eczema

How To Deal With Rosacea and Eczema

Rosacea and Eczema are two skin conditions that are fairly commonly found throughout the world. Each of them is characterized by different features, and can be both discomfiting as well as result in undesirable appearance features. In a nutshell, theyre problems that many would want to deal with.

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