INHIBITION OF PRIMARY MURINE MACROPHAGE CYTOKINE PRODUCTION IN-VITRO FOLLOWING TREATMENT WITH THE KAPPA-OPIOID AGONIST U50,488H

Previous work in our laboratory has shown that both mu- and kappa-opio id agonists exhibit immunosuppressive activity for antibody responses in vitro. Our earlier work has suggested that both accessory cells and T cells may be altered following treatment with the kappa-opioid agon ist U50,488H. We intend to further determine the identity of the immun e cell population(s) which are affected by opioid treatment, and to de termine the nature of the opioid receptor type expressed on these cell s. In this study, non-elicited peritoneal macrophages were treated sim ultaneously with the kappa-agonist U50,488H and lipopolysaccharide (LP S), and the levels of the cytokines interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF)-alpha were determined. The results show that U5 0,488H had a suppressive effect on the production of TNF-alpha and IL- 1 at concentrations as low as 1 nM, while IL-6 was suppressed at conce ntrations as low as 10 nM. Additional experiments utilizing the opiate antagonist naloxone and the kappa-selective antagonist norbinaltorphi mine (norBNI) were performed in order to further characterize the opio id receptor involved in the cytokine suppression produced by treatment with U50,488H. Results showed that naloxone was able to partially blo ck U50,488H suppression while norBNI was able to completely reverse th e suppression of IL-6 production. These results suggest that macrophag e/monocyte function is significantly modulated following activation of the kappa-opioid receptor.