Opposing activities of brain opioid receptors in the regulation of humoral and cell-mediated immune responses in the rat

The role of brain delta- and kappa-opioid receptors in the regulation of PFC response, Arthus hypersensitivity reactions and delayed hypersensitivity reactions was studied following intracerebroventricular (i.c.v.) administration of opioid receptor agonists and antagonists. Eight-week-old male Wistar rats, with polyethylene cannulae inserted into the lateral brain ventricles, were i.c.v. treated with different doses of delta-opioid receptor agonist methionine-enkephalin (Met-Enk), delta-opioid receptor antagonist ICI 174864, kappa-opioid receptor agonist MR 2034, and kappa-opioid receptor antagonist MR 2266. In rats sensitized for plaque-forming cell (PFC) assay, the first drug injection was given 1 h prior to immunization, and then every 24 h until day 4. One h after the last treatment, rats were sacrificed and (PFC) assay performed. In rats immunized for hypersensitivity skin reactions, the first drug injection was given 1 h before immunization, and then every 48 h until day 14. Skin reactions were elicited one h after the last drug administration. Opioid receptor agonists Met-Enk and MR 2034 stimulated and suppressed PFC response, Arthus and delayed skin reactions respectively. ICI 174864 decreased the number of PFC and intensity of hypersensitivity skin reactions whereas MR 2266 increased the number of PFC, but did not affect to a greater extent hypersensitivity reactions. Stimulation of PFC produced by 1 μg/kg of Met-Enk was completely blocked with 10 and 50 μg/kg of ICI 174864. MR 2034-induced suppression was partially and completely antagonized with 10 and 50 μg/kg of MR 2266 respectively. The present results suggest that brain opioid receptors differentially affect humoral and cell-mediated immune responses.