INCREASED ARGININE-VASOPRESSIN SECRETION MAY PARTICIPATE IN THE ENHANCED SUSCEPTIBILITY OF LEWIS RATS TO INFLAMMATORY DISEASE

Lewis (LEW/N) and Fischer (F344/N) rats are histocompatible inbred str ains characterized respectively by susceptibility and resistance to in flammatory disease. LEW/N rats have deficient corticotropin-releasing hormone (CRH), ACTH and corticosterone responses to inflammation, and increased circulating and hypothalamic concentrations of arginine vaso pressin (AVP). CRH is produced locally at inflammatory sites, where it acts as a proinflammatory agent, while AVP has been reported to exert immunopotentiating effects in vivo and in vitro. In order to further investigate the mechanism of increased AVP secretion in LEW/N rats, we measured AVP and CRH mRNA in several hypothalamic nuclei in LEW/N and F344/N rats, using in situ hybridization histochemistry. LEW/N rats h ad increased AVP mRNA concentrations in the supraoptic (SON) and parav entricular (PVN), but not in the suprachiasmatic (SCN) nuclei. CRH mRN A, on the other hand, was decreased in the PVN of LEW/N rats. To exami ne the potential role of AVP and CRH in the exaggerated inflammatory r esponses of LEW/N rats, we pretreated young female Lewis and Fischer r ats with AVP- and/or CRH-neutralizing rabbit antisera and elicited sub sequently an inflammatory response by a nuchal subcutaneous injection of carrageenin. We demonstrated that both antisera decreased significa ntly the leukocyte concentration in the inflammatory exudate in LEW/N rats, but found no synergistic or additive effects between them. We co nclude that previously observed differences in hypothalamic AVP and CR H contents between LEW/N and F344/N rats correspond to differences in the steady state mRNA levels of the two neuropeptides and that both AV P and CRH participate in the excessive inflammatory response of Lewis rats as locally active proinflammatory agents.