Lung monocyte/macrophage population dynamics following the combination of tobacco smoke, chronic morphine administration, and HIV infection in humanized mice

It is apparent that both opiate abuse, and tobacco smoking, are prevalent among HIV-infected individuals in the United States. We have previously shown that smoke exposure, HIV infection and chronic morphine administration accelerates the decline in circulating CD4 + T cells, and promotes the activation of brain microglial cells. In the present studies we wished to determine the impact of these three insults on inflammatory macrophages and monocytes in the lungs. Our results show that smoke exposure elevates the numbers of alveolar macrophages, but when animals also received a combination of HIV infection and/or morphine, the smoke-induced elevation in alveolar macrophages was reversed. The three insults, either alone or in combination, significantly reduced the numbers of interstitial macrophages, suggesting that these insults target the integrity of the monocyte/macrophage inflammatory system. Most notably, the combination of smoke exposure and HIV infection, much more than either insult alone, induced the most profound effects on both lung-associated and circulating monocytes. We believe this study is the first to examine the influences of the combination of smoke, chronic opiate exposure, and HIV infection on the monocyte/macrophage arm of the immune system. These findings are particularly significant given the clinical intersection of these three insults.