Morphine modulation of plasmodial-antigens-induced colony-stimulating factors production by macrophages.
Morphine abuse is known to cause immunosuppression and enhanced host susceptibility to malaria. We studied the effect of morphine on the Plasmodium berghei total-parasite-antigens soluble in culture medium (P.b.SA)-induced production of colony-stimulating factors (CSFs) by mouse peritoneal macrophages, in vitro. Morphine exerted a concentration-dependent biphasic modulatory effect; at 1 x 10(-4)-1 x 10 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 10(-12) M concentration the augmenting effect of morphine was significantly (p<0.05) diminished. Selective agonists of delta- (DPDPE) and mu- (DAGO) opioid receptors also respectively, inhibited and augmented the production of CSFs. The CSFs appear to be synthesized de novo as cycloheximide (50.0 microg/ml) completely inhibited their production. Naloxone ( 1 x 10(-5) M) lacked any 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 significantly (p<0.05) blocked the augmenting effect of morphine. These results suggest that morphine via opioid receptors, in a concentration-dependent biphasic manner, modulated the P.b.SA-induced de novo production of CSFs by macrophages, in vitro.
Singh
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Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Nagar, India. niper@chd.nic.in
Singh
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D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000276:immunology / Q000494:pharmacology*; D000818:Animals; D000953:Antigens, Protozoan / Q000096:biosynthesis*; D003115:Colony-Stimulating Factors / Q000096:biosynthesis*; D003513:Cycloheximide / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D004347:Drug Interactions; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology; D005260:Female; D007700:Kinetics; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009020:Morphine / Q000276:immunology / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010962:Plasmodium berghei / Q000276:immunology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000819:agonists; D017450:Receptors, Opioid, mu / Q000819:agonists
D000276:Adjuvants, Immunologic; D000701:Analgesics, Opioid; D000953:Antigens, Protozoan; D003115:Colony-Stimulating Factors; D009292:Narcotic Antagonists; D011500:Protein Synthesis Inhibitors; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-; D003513:Cycloheximide