Interferon-α reduces catecholamine secretion from bovine adrenal chromaffin cells stimulated by acetylcholine

Abstract

A long-term pretreatment (72h) of bovine adrenal chromaffin cells with recombinant human interferon (IFN)-α-2b (1500 units/ml) produced a decrease in the secretion of catecholamines from the cells stimulated by acetylcholine (ACh) (25μmol/l) but not that with human fibloblast IFN-β (3000 units/ml) or recombinant human IFN-γ (3000 units/ml). IFN-α-2b inhibited the ACh-induced secretion in a concentration- (30–1500 units/ml) and time-dependent manner (18–72h). The content of catecholamines in the cells treated with IFN-α-2b for 72h did not change. The inhibitory effect of IFN-α-2b on the secretion was abolished when the cells were simultaneously treated with anti-IFN-α antibody, and it was overcome by the increase in the external ACh concentration. IFN-α-2b also inhibited ACh-induced Ca²⁺ influx into the cells in a concentration-dependent manner similar to that of the IFN-α-2b inhibiting ACh-induced secretion. On the other hand, IFN-α-2b failed to reduce the secretion from the cells induced by high K⁺. These results strongly suggest that IFN-α-2b reduces the ACh-induced secretion of catecholamines from bovine adrenal chromaffin cells due to modulating the gene expression of the nicotinic ACh receptor-operated cation channels rather than due to directly affecting the channels. The results further indicate that the IFN-α-2b inhibition may be associated with the psychiatric side effects of IFN-α (depression, neurasthenica and somnolence, etc.), and that immune systems may regulate the function of (autonomic) nervous systems or adrenal medulla via IFN-α in vivo.