THE EFFECT OF INTERFERON-ALPHA ON THE PITUITARY-ADRENAL AXIS

This report concerns the use of a minimum stress animal model for eval uating the neuromodulatory effects of interferon-alpha (IFN-alpha), Ma le Sprague-Dawley rats, 350-450 g, received jugular catheters and were habituated to handling and sampling arenas, These procedures will min imize stress usually associated with i.v. injections and blood samplin g, Natural rat IFN-alpha/beta (RaIFN-alpha/beta) endotoxin free (Lee B iomolecular Research Laboratories, San Diego, CA) or recombinant human IFN-alpha (rHuIFN-alpha) (a gift from Hoffman La Roche, Nutley, NJ) w as injected into rats via catheter at various IFN concentrations, Cont rols were injected with either (1) vehicle (saline), (2) human or bovi ne serum albumin in saline, or (3) heat-denatured RaIFN-alpha/beta. Ex periments were begun (0 h) at about 0900 h, and blood samples were wit hdrawn at intervals up to 2 h after IFN or control injections and repl aced by the same volume of saline, The concentrations of corticosteron e and ACTH in peripheral plasma were measured by radioimmunoassay, Bot h IFN, when injected at concentrations of 300 or 600 U/g body weight ( U/gbw), stimulated an increase above 0 h levels of both hormones in th e same animals, Additionally, the stimulation was also evident when co mpared with plasma hormone levels in animals injected with control sub stance in a parallel time course, After administration of 150 U/gbw of either IFN, only the increase in the blood corticosterone was signifi cant, These studies demonstrate that both homospecific (RaIFN-alpha/be ta) and heterospecific (rHuIFN-alpha) IFN preparations are capable of stimulating the pituitary-adrenal axis.