naloxone and Tuberculosis--Pulmonary

Topics: Adult; Aged; Chromatography, Gas; Drug Interactions; Feces; Female; Heroin Dependence; Humans; Liver; Male; Mass Spectrometry; Methadone; Methods; Middle Aged; Naloxone; Rifampin; Substance Withdrawal Syndrome; Tuberculosis, Pulmonary

The effects of opiates in various infections are well known; however, very little is known about tuberculosis infection. Therefore, in the present study, we report for the first time, the effects of morphine during murine tuberculosis. Mice were infected intravenously with Mycobacterium tuberculosis H37Rv, administered morphine (0.1-100 mg/kg subcutaneously on day 0 and day +15) and sacrificed on day +30 for CFU enumeration in lungs and spleen. Morphine exerted maximum suppression of infection at 5 mg/kg, and sometimes completes elimination of infection; naloxone, silica and aminoguanidine blocked the protective effect of morphine. In vitro, morphine lacked direct antimycobacterial activity up to 1x10(-4) M concentration, as assessed by radiometric BACTEC method. In macrophage model of infection, morphine showed maximal killing at 1x10(-7) M concentration, the activity was blocked by naloxone and aminoguanidine. These observations suggest that morphine exerts a dose-dependent effect in murine tuberculosis, the protective effect being naloxone-reversible and may involve macrophage-mediated protective mechanisms. These results may be helpful in developing new opioid-like chemical entities against tuberculosis infection.

Topics: Analgesics, Opioid; Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Guanidines; Injections, Subcutaneous; Lung; Macrophages, Peritoneal; Male; Mice; Morphine; Mycobacterium tuberculosis; Naloxone; Neuroimmunomodulation; Silicon Dioxide; Spleen; Tuberculosis, Pulmonary; Tuberculosis, Splenic