OPIOID RECEPTOR-MEDIATED SUPPRESSION OF HUMORAL IMMUNE-RESPONSE IN-VIVO AND IN-VITRO - INVOLVEMENT OF KAPPA-OPIOID RECEPTORS

The selective kappa opioid receptor agonist MR 2034 exerted pronounced suppression of plaque-forming cell (PFC) response following intraperi toneal (i.p.) administration in the rat. Pretreatment with preferentia l kappa and mu opioid receptor antagonists MR 2266 and naloxone, respe ctively, revealed that this effect was mediated mainly by kappa, and t o a low extent by mu opioid receptors. Intracerebroventricular (i.c.v. ) administration of quaternary naltrexone (QNtx) moderately attenuated , whereas i.p. given QNtx completely prevented the suppressive effect of MR 2034, suggesting a peripheral mechanism of action, and only mino r involvement of brain opioid receptors. MR 2034 markedly decreased th e PFC response of spleen cells obtained from in vivo immunized rats, t reated in vitro with the opiate. The immunosuppressive action of MR 20 34 in vitro was completely and partially blocked by equimolar concentr ations of MR 2266 and naloxone, respectively. Antagonists alone produc ed stimulation of PFC following i.p. administration in the rat, but di d not affect PFC response upon in vitro treatment. These results sugge st that peripheral kappa opioid receptors down-regulate primary humora l immune response in the rat, and that this effect may be produced by direct interference with plasma cell activity.