IMMUNOMODULATION INDUCED BY INTRAPERITONEAL AND INTRACEREBROVENTRICULAR INJECTIONS OF ENKEPHALINASE INHIBITOR DES-TYROSINE(1)-METHIONINE-ENKEPHALIN, AND ABROGATION OF THE EFFECT BY OPIOID ANTAGONISTS NALOXONE AND NALTREXONE

We have previously shown that exogenous methionine-enkephalin, applied peripherally and centrally, induced a dose-dependent immunomodulation . The present study deals with the interaction of the enkephalinase-in hibitor des-tyrosine methionine-enkephalin and opioid antagonists nalo xone and naltrexone, in relation to a humoral immune response, the pla que-forming cell response in the rat For this purpose rats were treate d intraperitoneally only with 0.2 and 1 mg/kg of des-tyrosine1-methion ine-enkephalin, or with des-tyrosine1-methionine-enkephalin in combina tion with subcutaneous injections of 5 mg/kg of naloxone, before and a fter immunization with sheep red blood cells. Other groups of animals were given intracerebroventricularly 20 and 200 mug/kg of des-tyrosine 1-methionine-enkephalin alone, or des-tyrosine1-methionine-enkephalin combined with intracerebroventricular treatment with 10 mug/kg of quat ernary naltrexone methylbromide. The last group was treated on the day of immunization and during 3 consecutive days. Experimental and contr ol groups were tested for plaque-forming cell response. The results sh owed that (a) in rats treated intraperitoneally with des-tyrosine1-met hionine-enkephalin there was a dose-dependent increase of humoral immu ne response, and this increase was abrogated by naloxone; and (b) in a nimals repeatedly injected intracerebroventricularly with des-tyrosine 1-methionine-enkephalin, the low dose (20 mug/kg) potentiated while th e high dose (200 mug/kg) suppressed the plaque-forming cell response, but these effects were completely abolished by i. c. v. administration of quaternary naltrexone. Thus, these results revealed the immunomodu latory activity of des-tyrosine1-methionine-enkephalin when given peri pherally or centrally, and a negative function of naloxone and quatern ary naltrexone on this activity. The finding that quaternary naltrexon e, an opioid antagonist that does not cross the blood-brain barrier, a brogates the central des-tyrosine1-methionine-enkephalin-induced immun e modulation, suggests the involvement of the CNS opioid system in imm unoregulation.