Treatment of lupus with corticosteroids

Through direct signals to the nucleus mediated by the glucocorticoid receptor, exogenous glucocorticoids impact a broad array of cellular functions. DNA binding of the glucocorticoid receptor, depending upon the specific promoter to which the receptor binds, affects gene expression by recruiting transcription factors to the promoter or by interfering with the function of co-factors required for gene transcription. Steroid effects on the adhesion functions and release of products by phagocytic cells are prompt, occurring within hours of administration. Administration of corticosteroids results in rapid depletion of circulating T-cells due to a combination of effects including enhanced circulatory emigration, induction of apoptosis, inhibition of T-cell growth factors, and impaired release of cells from lymphoid tissues. Corticosteroid effects on B-cell function and immunoglobulin production are more delayed. The broad, generally suppressive effects of corticosteroids on the immune response render them useful for the management of most organ system manifestations of lupus. Corticosteroid toxicity in lupus is notable for greater susceptibility to infections, osteoporosis, osteonecrosis and accelerated atherogenesis. Although use of corticosteroids for patients with severe disease manifestations is associated with higher numbers of deaths from infections, overall survival appears to be improved.