INTERLEUKIN-12 THERAPY RESTORES CELL-MEDIATED-IMMUNITY IN ETHANOL-CONSUMING MICE

Previous studies from our laboratory show that ethanol consumption imp airs antigen-specific, cell-mediated, but not, humoral immune response s of C57BL/6, BALB/c, and DO11.10 T-cell receptor transgenic mice. Thi s ethanol-associated deficit is associated with decreased interleukin (IL)-12 and interferon-gamma (IFN-gamma) production, but not IL-2 or a ntigen-specific T-cell proliferation by explanted leukocytes from etha nol-consuming mice. IL-12 expression by macrophage/monocytes is viewed as a requirement for the production of IFN-gamma by Th1 lymphocytes t hat mediate cellular immunity. In this study, we restored antigen-spec ific, cell-mediated immunity, delayed hypersensitivity, to ethanol-con suming C57BL/6 or BALB/c mice with a single 100 ng of intravenous inje ction of recombinant IL-12 at the time of immunization. The addition o f exogenous recombinant IL-12 to cc-cultures of antigen-presenting cel ls derived from ethanol-consuming mice and purified T cells derived fr om ethanol-nonconsuming DO11.10 repairs the ability of Th1 cells to ma ke IFN-gamma in response to antigen. Administration of recombinant IL- 12 opens a potential for restoring cell-mediated immune function to et hanol-consuming individuals.