Neuroimmunomodulatory effects of morphine in Leishmania donovani-infected hamsters.
OBJECTIVE
The effect of morphine on host defense during Leishmania donovani infection in golden hamsters was studied.


METHODS
Hamsters were intracardially infected with L. donovani amastigotes and then monitored by spleen touch print microscopic examination. Morphine and naloxone were administered subcutaneously and intraperitoneally, respectively. Leukocytes were counted by a hemocytometer, and ex vivo phagocytosis was determined by the examination of stained adherent macrophages.


RESULTS
Low doses of morphine, 1.75 and 2.5 mg/kg x 2, administered subcutaneously on day 0 and day 15 significantly (p < 0.05) suppressed the infection, whereas high doses (20.0 and 50.0 mg/kg x 2) exacerbated the infection. On day 30, hamsters treated with low doses of morphine showed a significant (p < 0.05) increase in the number of circulating leukocytes and the pool size and phagocytic activity of peritoneal macrophages ex vivo; in hamsters treated with high doses, all these parameters appeared to be diminished. The bone marrow of morphine-treated hamsters showed a fall in total cellularity and no change in the number of monocytes; however, in those treated with low doses, the infection was completely eliminated by day 30, and paradoxically, a significant (p < 0.05) potentiation of infection was observed in hamsters treated with high doses. The spleens of hamsters treated with both low and high doses of morphine showed a significant (p < 0.05) decrease and increase in weight, respectively; treatment with low doses also caused an almost 2-fold increase in the percentage of monocytes. Morphine apparently exerted its protective effects via naloxone-sensitive opioid receptors; naloxone pretreatment did not affect the potentiation of infection.


CONCLUSIONS
Conditional doses of morphine apparently biphasically modulated the course of L. donovani infection in hamsters, at least in part through macrophage-mediated mechanisms.
Singal
Priya
P
Department of Biotechnology, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, India.
Kinhikar
Arvind G
AG
Singh
Savita
S
Singh
Prati Pal
PP
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D006224:Cricetinae; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007893:Leishmania donovani; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000276:immunology* / Q000503:physiopathology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D008647:Mesocricetus; D009020:Morphine / Q000008:administration & dosage*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000008:administration & dosage; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D011957:Receptors, Opioid / Q000819:agonists / Q000378:metabolism; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D007166:Immunosuppressive Agents; D009292:Narcotic Antagonists; D009294:Narcotics; D011957:Receptors, Opioid; D009270:Naloxone; D009020:Morphine