MECHANISMS OF GLUCOCORTICOID ACTION ON IMMUNE PROCESSES

Glucocorticoids have a multitude of effects on many of the stages in inflammatory and immune processes. In general, corticosteroids have greater effects on leukocyte traffic than on function, and they have more effect on cellular than humoral processes. Probably the most important physiological and clinical effect of corticosteroid administration in humans is their ability to inhibit the recruitment of neutrophils and monocyte-macrophages to an inflammatory site. It is this mechanism that probably accounts for the increase in infections seen with daily corticosteroid therapy. Of note is the fact that alternate-day corticosteroids do not inhibit recruitment of neutrophils and are not associated with an increased infection rate. Glucocorticoids produce a marked lymphocytopenia secondary to a redistribution of lymphocytes out of the circulation to other lymphoid compartments; this redistribution selectively affects T lymphocytes more than other populations. Glucocorticoids suppress delayed hypersensitivity skin testing by blocking the recruitment of monocyte-macrophages by sensitized T lymphocytes. Corticosteroids can inhibit a variety of functional capabilities of the lymphocyte and probably produce complex regulatory effects on suppressor and helper cell populations. Monocyte-macrophage function is relatively sensitive to the effects of glucocorticoids and this sensitivity probably accounts for many glucocorticoid suppressive effects. Neutrophil function is relatively resistant to these agents. Glucocorticoid effects on immunoglobulin synthesis and complement metabolism are not felt to be clinically significant. However, corticosteroids have an important inhibitory effect on reticuloendothelial clearance of antibody-coated cells. Corticosteroid potentiation of the action of catecholamines and prostaglandins may have importance in certain disease states. Corticosteroids are important and widely used therapies in the treatment of a large number of inflammatory and immunologically mediated diseases. Continued advances in understanding of the mechanisms of action of these agents should allow their more rational and effective use in clinical settings.