Effects of interferons on cortisol production in bovine adrenal fasciculata cells stimulated by adrenocorticotropin

The effects of interferons (IFNs) IFN-alpha, IFN-beta and IFN-gamma on the production of cortisol in bovine adrenal fasciculata cells have been invest igated. Pretreatment of the fasciculata cells with recombinant interferon-alpha-2b from man (over 300 units mL(-1)), but not with fibroblast IFN-beta or recom binant IFN-gamma from man, reduced the production of cortisol in cells stim ulated with adrenocorticotropin (ACTN) (1 nM). IFN-alpha-2b inhibited ACTH- induced cortisol production in a concentration- (300-15 000 units mL(-1)) a nd time- (2-24 h) dependent manner. The inhibitory effect of IFN-alpha-2b o n the production was abolished when the cells were simultaneously treated w ith anti-IFN-alpha antibody, and it was reversible. IFN-alpha-2b also inhib ited dibutyryl cyclic AMP-induced production of cortisol but not pregnenolo ne-induced production. The effect of IFN-alpha-2b was not influenced by inc reases in external ACTH and Ca2+ concentrations and IFN-alpha-2b did not af fect the ACTH-induced increase in cyclic AMP level in the cells. These results strongly suggest that IFN-alpha-2b reduces ACTH-induced produ ction of cortisol in bovine adrenal fasciculata cells by affecting the earl y process of cortisol synthesis. The results also indicate that IFNs might not directly affect steroidogenesis in the adrenal cortex in-vivo, because of the requirement of high concentrations of IFN-alpha-2b for inhibition, a nd because of the ineffectiveness of IFN-beta and IFN-gamma.