The Biologic Activity of ACTH and Related Peptides on Peripheral Blood Mononuclear Cells Is Altered by the Presence of Dexamethasone

We wished to determine whether the glucocorticoid hormone dexamethasone (dex), a potent modulator of both pituitary-adrenal and immunologic activity, altered the effect of adrenocorticotropin-related peptides on activated peripheral blood mononuclear cells (PBMCs) and T-cells. PBMCs preactivated with Concanavalin A (Con A) and T-cells preactivated with phorbol 12, 13 dibutyrate (PDB) plus phytohemagglutinin (PHA) were exposed to dex, ACTH, and related peptide sequences. Proliferation of cells was measured as was IL-2 in conditioned media. It was found that in the absence of dex only the peptide ACTH(18-39) altered proliferation of PBMCs while there was no effect of peptide on T-cells activated via protein kinase C-mediated pathways. Significant reversal of the inhibitory effect of dex on proliferation of PBMCs exposed to Con A was achieved with addition of ACTH(1-39) and ACTH(11-24), while IL-2 levels were unaffected by the addition of peptide. ACTH(18-39) and ACTH(11-24) enhanced the inhibitory effect of dex on T-cells activated with PDB plus PHA. These findings suggest that the biologic activity of ACTH on immune cells is altered when dexamethasone is present and under certain circumstances ACTH may protect the immunologic response from the inhibitory effects of elevated ambient glucocorticoids.