Monocyte aberrations are characteristic of the immune response following in vivo or in vitro ethanol uptake. Elevated production of MO prostaglandin E2 (PGE2), one of several ethanol induced MO aberrations, has also been identified as pivotal in the mediation of post-trauma immunosuppression. Alcohol consumption before trauma acts synergistically with injury to effectuate immunosuppression. Our long term goal is to identify the altered monocyte functions in response to ethanol which lead to more severe immuno-suppression after injury. The trauma patients represent an excellent model to discern how ethanol affects an already immunosuppressed immune system. We have demonstrated that a disproportionate increase in a particular inhibitory MO subset is largely responsible for the post-trauma elevation of immunosuppressive PGE2, high levels of tumor necrosis factor (TNF), elevated interleukin 6 (IL-6) production, as well as antigen presenting capacity. Consequently, a post-trauma increase in this subset at the expense of the facilitory MO subset could explain many of the post- injury aberrant MO functions. Our hypothesis is that ethanol depresses the immune system by mechanisms similar to those seen in immunosuppressed trauma patients. Additionally, ethanol may interact with other pathways to increase immune depression in immunocompromised patients such as post- injury and AIDS patients. We further postulate that the shift in the FcRI MO subsets may result from altered monokine/lymphokine levels in the alcoholic and post-trauma microenvironment which preferentially cause differentiation and/or activation of particular MO subsets. First, we propose to examine, in normals and non-alcoholic trauma patients, the in vitro effect of ethanol on inhibitory monokine (PGE2 and TGFBeta) and inflammatory monokine (IL-6, TNF, IL-1) production, as well as on MO antigen presentation capacity (APC). Second, in order to study the in vivo effect of ethanol, we propose to monitor and analyze these monocyte functions (IL-6, TNF, IL-1, PGE2, TGFBeta levels, and APC) in normals, as well as in three trauma patient groups: trauma patients without alcohol uptake, trauma patients with single ethanol preexposure and chronic alcoholic patients with trauma. We will determine the distribution of these groups' MO subsets separated on the basis of their FcRI, FcRII, CD14 and CD4 surface antigen expression. The in vivo effect of ethanol on MO functions will also be assessed in alcoholic, non-trauma patients. Finally, since ethanol may predispose for preferential maturation of certain MO subsets, we will examine the in vitro effect of ethanol on the differentiation of MO subsets from the myeloblastic cell lines KG-1 AND PLB-985.
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