Central Corticotropin-Releasing Factor Mediates the Suppressive Effect of Stress on Natural Killer Cytotoxicity*

CRF acts within the brain to elicit changes in neuroendocrine, autonomic, and behavioral activity similar to that observed after stress. A reduction of splenic natural killer (NK) activity has also been described after the central administration of CRF. In this study we examined whether the central release of CRF plays a physiological role in mediating stress-induced suppression of NK cytotoxicity. Four sessions of footshock stress (1.5 mamp; 1-sec duration; 60-Hz sine wave; delivered randomly twice per min for 30 min) over a 48-h period significantly (P less than 0.001) reduced splenic NK activity in the rat. Pretreatment of the animals by central administration of polyclonal CRF antibodies completely antagonized the stress-induced suppression of NK cell activity. In contrast, the peripheral immunoneutralization of CRF was ineffective. Measurement of circulating levels of ACTH and corticosterone demonstrated that stress-induced elevations of ACTH and corticosterone were significantly (P less than 0.05) attenuated by peripheral anti-CRF serum, but not by centrally administered anti-CRF. These findings suggest that endogenous brain CRF coordinates the suppressive effect of footshock stress on NK cytotoxicity independently of pituitary-adrenal activation.