title: Central corticotropin-releasing factor mediates the suppressive effect of stress on natural killer cytotoxicity.
abstract: 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.
authors.affiliation: Department of Psychiatry, San Diego Veterans Administration Medical Center 92161.
authors.forename: M
authors.initials: M
authors.lastname: Irwin
authors.forename: W
authors.initials: W
authors.lastname: Vale
authors.forename: C
authors.initials: C
authors.lastname: Rivier
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000276:immunology / Q000502:physiology*; D003602:Cytotoxicity, Immunologic; D004597:Electroshock; D007106:Immune Sera / Q000008:administration & dosage / Q000494:pharmacology; D007116:Immunization, Passive; D007276:Injections, Intraventricular; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000276:immunology; D013312:Stress, Physiological / Q000276:immunology*
chemical_list: D007106:Immune Sera; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone