Effects of immune neutralization of corticotropin-releasing hormone, adrenocorticotropin, and beta-endorphin in the surgically stressed rat.
Specific in vivo neutralization was used in an attempt to explore the roles of corticotropin-releasing hormone (CRH), ACTH, and beta-endorphin during surgical stress in Sprague-Dawley rats. Rats were randomly assigned to groups (n = 20-30/group) that received iv injections of rabbit antirat/human CRH (anti-r/hCRH), antihuman ACTH (anti-hACTH), antihuman beta-endorphin (anti-h beta-endorphin), or normal rabbit serum. Three hours later all animals were subjected to a uniform stress consisting of ether anesthesia, surgical laparotomy, and phlebotomy of 7 ml via the inferior vena cava. Survival rates were recorded, and RIAs were performed for ACTH, beta-endorphin, and corticosterone. Rats treated with anti-h beta-endorphin had a survival rate of 64%, which was significantly higher than that of the control group (33%; P less than 0.025, by analysis of variance). Anti-r/hCRH or anti-hACTH treatment was not associated with a change in survival rate. Plasma immunoreactive beta-endorphin levels were markedly decreased in the group treated with anti-h beta-endorphin (P less than 0.0001). Anti-r/hCRH had no effect on plasma immunoreactive ACTH or beta-endorphin. Plasma immunoreactive ACTH and corticosterone levels were decreased in the group treated with anti-hACTH (P less than 0.0001 and P less than 0.01, respectively). We conclude that 1) beta-endorphin immune neutralization is associated with a survival advantage during severe surgical stress, suggesting that circulating beta-endorphin might have deleterious effects during stress; 2) In severe stress, acute immune neutralization of CRH is not sufficient to inhibit ACTH, beta-endorphin, and corticosterone secretion, suggesting significant involvement of other secretagogues of the pituitary-adrenal axis; and 3) moderate decreases in corticosterone cannot affect survival, presumably because glucocorticoids play only a permissive role in maintaining cardiovascular stability during surgical stress.
Giuffre
K A
KA
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
Udelsman
R
R
Listwak
S
S
Chrousos
G P
GP
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000276:immunology / Q000502:physiology*; D000818:Animals; D000936:Antigen-Antibody Complex; D003346:Corticotropin-Releasing Hormone / Q000097:blood / Q000276:immunology / Q000502:physiology*; D003429:Cross Reactions; D007106:Immune Sera; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013312:Stress, Physiological / Q000503:physiopathology*; D001615:beta-Endorphin / Q000097:blood / Q000276:immunology / Q000502:physiology*
D000936:Antigen-Antibody Complex; D007106:Immune Sera; D001615:beta-Endorphin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone