Morphine modulation of plasmodial-antigens-induced colony-stimulating factors production by macrophages

Morphine abuse is known to cause immunosuppression and enhanced host suscep tibility to malaria. We studied the effect of morphine on the Plasmodium be rghei total-parasite-antigens soluble in culture medium (P.b.SA)-induced pr oduction of colony-stimulating factors (CSFs) by mouse peritoneal macrophag es, in vitro. Morphine exerted a concentration-dependent biphasic modulator y effect; at 1 x 10(-4)-1 x 10(-6) M it slightly inhibited, whereas at 1 X 10(-8)-1 X 10(-10) M it augmented the production of CSFs. However, at 1 X 1 0(-12) M concentration the augmenting effect of morphine was significantly (p<0.05) diminished. Selective agonists of delta-(DPDPE) and mu-(DAGO) opio id receptors also respectively, inhibited and augmented the production of C SFs. The CSFs appear to be synthesized de novo as cycloheximide (50.0 mu g/ ml) completely inhibited their production. Naloxone (1 X 10(-5) M) lacked a ny effect on the inhibitory effect of morphine; however, at 1 X 10(-3) M it exerted partial blocking effect. Conversely, at 1 X 10(-5) M naloxone sign ificantly (p<0.05) blocked the augmenting effect of morphine. These results suggest that morphine via opioid receptors, in a concentration-dependent b iphasic manner, modulated the P.b.SA-induced de novo production of CSFs by macrophages, in vitro. (C) 2000 Elsevier Science Inc. All rights reserved.