ETHANOL--SUPPRESSION OF MYCOBACTERIAL RESISTANCE

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Heavy use of alcohol is associated with an increase risk of respiratory disease and of tuberculosis and may be associated with the increased incidence of Mycobacterial disease associated with human immunodeficiency virus infection. As many as 50% of the individuals who have died of AIDS have been infected with Mycobacterium avium. This work is an extension of work in my laboratory that has shown that the differential expression of MHC class II glycoproteins by both murine macrophages and human monocytes may be related to differences in the innate state of activation of macrophages and differences in resistance to Mycobacteria] infection. To accomplish our goals we will take advantage of a model for Mycobacterial disease that utilizes congenic strains of mice that are resistant or susceptible to the in vivo growth of Mycobacteria. Studies have shown that consumption of ethanol or treatment of macrophages in vitro with ethanol results in the suppression of anti-mycobacterial resistance. To understand the role of ethanol on the increased susceptibility to Mycobacterial growth we will: Determine the effect of ethanol consumption on the growth of Mycobacterium avium in the spleen and lung of infected mice; determine the effect of ethanol consumption on macrophage mediated anti-mycobacterial mechanisms and determine the effect of in vitro ethanol treatment on the antimycobacterial activity of splenic and lung macrophages including their response to cytokines.