Multiple mechanisms of B cell immunoregulation in man after administration of in vivo corticosteroids.

Abstract

Despite the extensive clinical use of corticosteroids (CS) in the treatment of immune-mediated diseases, relatively little is known concerning the effects of CS on B cell function as measured by in vitro assays. The effects of single-dose vs several days of in vivo CS therapy on the spontaneous and mitogen-induced Ig production by human peripheral blood B cells are reported here. Spontaneous Ig production by individual B cells was enhanced by in vivo CS as measured by an in vitro plaque-forming cell (PFC) assay. The same increased response was also observed with a brief in vitro exposure of the B cells to CS, which suggests that a mere brief exposure to an active CS analogue is all that is required to produce the enhanced response. The immunoregulatory effects of in vivo CS on mitogen-induced Ig production are more complex. Pokeweed mitogen-induced PFC responses were suppressed 4 to 5 hr after a single in vivo pharmacologic dose of CS, with complete recovery by 24 hr. In contrast, after a 5-day course of CS, the suppressed PFC response did not recover until 60 hr after the last dose. Moreover, several mechanisms of suppression were operative. Ten hours after completing the 5-day course of CS, there was a relative enrichment in the peripheral blood compartment of lymphocytes bearing the OKT8 suppressor/cytotoxic T cell phenotype that coincided with a depressed PFC response. At 36 hr after the last dose, the T lymphocyte profile returned to normal while B cell function remained suppressed. The complex, multifaceted modulation of the immune response, resulting from redistribution of cell subsets as well as altered cell functions, vary with time-dose parameters of in vivo CS administration. These observations should provide additional insights into the heterogeneity of CS-induced therapeutic effects.