Neuroimmunomodulatory Effects of Morphine in <i>Leishmania donovani</i>-Infected Hamsters

Abstract

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 × 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 × 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. Conclusion: Conditional doses of morphine apparently biphasically modulated the course of L. donovani infection in hamsters, at least in part through macrophage-mediated mechanisms.

Effect of morphine on Mycobacterium smegmatis infection in mice and macrophages

“…Opioids can modulate the in vivo course of parasitic and bacterial infections in a dose-dependent manner [8,9,11,15,20]. In the present study, we report, apparently M. smegmatis-infected mice were treated with indicated doses of morphine on day 0 and day +3 and sacrifi ced to determine bacterial load in lungs and spleen as described in Materials and methods.…”

“…Previous reports on immunomodulatory activity of morphine have demonstrated the protective effects of low doses of morphine in experimental models of malaria [11], leishmania [8,9] and TB [15]. However, relatively higher doses of morphine were found to be protective in M. smegmatis infection in vivo.…”

“…Elicited peritoneal macrophages were harvested from mice as described elsewhere [9]. Adherent macrophage monolayers were infected with M. smegmatis as described elsewhere [15] and incubated with different concentrations of morphine (1 pM to 100 μM) in presence or absence of 10 μM naloxone and 100 μM AG.…”

“…Morphine can augment protective immune responses, both in vitro and in vivo, leading to suppression of infection [6][7][8]. The effects observed are dose-dependent and biphasic in nature [8][9][10][11].…”

“…Recently, we have reported the protective effects of morphine in M. tuberculosis infection in mice and macrophages [15]. The protective role of opioids may result from macrophage activation at lower concentrations leading to enhanced production of cytokines and nitric oxide (NO) [3,[8][9][10][11]15]. These molecules play a crucial role in intramacrophage and in vivo killing of mycobacteria as well [15][16][17][18].…”