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.