Glucocorticoids Inhibit Macrophage Proteinase Secretion

Glucocorticoids have a major role in the therapy of inflammatory and immunologically mediated diseases. The precise mechanism of the suppressive and anti-inflammatory effects of these drugs is still unknown, but the functions of the mononuclear phagocyte system are generally believed to be sensitive to glucocorticoid action (1-3). During glucocorticoid administration in vivo, monocytopenia occurs (4-6) and monocytes fail to accumulate at inflammatory sites (7-10). In the presence of glucocorticoids, macrophages do not respond to macrophage migration inhibitory factor (11), and fail to become "armed" or activated (8, 11-13). In experiments in vivo it is difficult to determine whether glucocorticoids are acting directly on macrophages or indirectly on lymphocytes and other cells that produce mediators of macrophage function (3, 8). Macrophages may serve as a direct target for the therapeutic actions of antiinflammatory steroids. In the accompanying paper (14), I establish that mononuclear phagocytes contain specific, high affinity receptors for glucocorticoids. In the present paper, I examine the action of glucocorticoids on biochemical functions of monocytes and macrophages cultured in vitro. Mononuclear phagocytes at all stages of maturat ion are sensitive to glucocorticoids. Production of monocytic and granulocytic colonies from bone marrow precursors and the secretion of elastase, collagenase, plasminogen activator, and nonspecific neutral proteinases by mature macrophages are inhibited by physiological concentrations of glucocorticoids. I have studied macrophages from glucocorticoidsensitive (rabbit, mouse) and glucocorticoid-insensitive (human, guinea pig) species, and all show similar glucocorticoid-mediated actions, even though they differ in hormone-mediated effects on lymphocytes (1, 3). Because steroid concentrations comparable to those for saturating the high affinity glucocorti-