Interferon Alpha Acts On Hypothalamic-Pituitary-Adrenal Axis By Two Different Receptor Mechanisms

Although interferon alpha (IFNα) is known to be involved in the regulation of hypothalamic-pituitary-adrenal Axis, yet its effect has not been consistently reproduced in different experiments and its receptor mechanism is not thoroughly characterized. In this study we employ two kinds of mutants of IFNα: 129Ser-IFNα and 38Leu-IFNα. The antiviral activity of 129Ser-IFNα almost disappeared, but there still retained the strong analgesic activity. The antiviral activity of 38Leu-IFNα remained, but the analgesic activity disappeared completely. In vivo study by intracerebroventricular administration of recombinant IFNα and opioid receptor antagonist naloxone to rats, Concentration of CRH, ACTH, and corticosterone in blood and ACTH from the supernatant of pituitary's homogenate were determined by RIA. In vitro experiments were performed using hypothalamus slices, AtT20 cells, a pituitary-derived cell line, and adrenal cortical slices. The production of CRH, ACTH, and corticosterone were examined respectively. The results showed that 129Ser-IFNα, wild IFNa together with morphine, the positive control, can modulate the HPA axis, and their effects can be blocked by naloxone. Meanwhile 38Leu-IFNα which is not correlated with opioid receptor can also act on the HPA axis but with less potency and not be influenced by naloxone. It is inferred that IFNα may modulate the HPA axis by at least two different receptor mechanisms: one of them is opioid receptor and the other maybe IFNα receptor.