Platelet-activating factor leukocyte effects

In addition to their effects on leukocyte function, glucocorticoids influence the inflammatory response by reducing the prostaglandin, leukotriene, and platelet-activating factor synthesis that results from activation of phospholipase - Finally, glucocorticoids reduce expression... 

Immunosuppressive agents, alone or in combination, are commonly used to alter the immune processes that are responsible for the glomerulonephritides. Corticosteroids, in addition to their immunosuppressive effecL also possess anti-inflammatory activities. They reduce the production and/or release of many substances that mediate the inflammatory process, such as prostaglandins, leukotrienes, platelet-activating factors, tumor necrosis factors (TNFs), and interleukin-1 (IL-1). Movement of leukocytes and macrophages to the site of inflammation is also inhibited. The immunosuppressive effects of corticosteroids are mediated through the inhibition of the release... 

Anti-inflammatory effects Glucocorticoids have a dramatic effect on the distribution and function of leukocytes. These drugs increase neutrophils and decrease lymphocytes, eosinophils, basophils, and monocytes. The migration of leukocytes is also inhibited. The biochemical mechanisms underlying these cellular effects include the induced synthesis of an inhibitor of phospholipase A2 (see Chapter 18), decreased mRNA for COX-2, decreases in IL2 and IL3, ind decreases in platelet activating factor (PAF), an inflammatory cytokine. 

The antiinflammatory effects of statins likely result from their ability to inhibit the formation of mevalonic acid. Downstream products of this molecule include not only the end product, cholesterol, but also several isoprenoid intermediates that covalently modify ( pre-nylate ) certain key intracellular signaling molecules. Statin treatment reduces leukocyte adhesion, accumulation of macrophages, MMPs, tissue factor, and other proinflammatory mediators. By acting on the MHC class II transactivator (CIITA), statins also interfere with antigen presentation and subsequent T-cell activation. Statin treatment can also limit platelet activation in some assays as well. All these results support the concept that in addition to their favorable effect on the lipid profile, statins can also exert an array of antiinflammatory and immunomodulatory actions. 

---