Interleukin-12 therapy restores cell-mediated immunity in ethanol-consuming mice.
Previous studies from our laboratory show that ethanol consumption impairs antigen-specific, cell-mediated, but not, humoral immune responses of C57BL/6, BALB/c, and DO11.10 T-cell receptor transgenic mice. This ethanol-associated deficit is associated with decreased interleukin (IL)-12 and interferon-gamma (IFN-gamma) production, but not IL-2 or antigen-specific T-cell proliferation by explanted leukocytes from ethanol-consuming mice. IL-12 expression by macrophage/monocytes is viewed as a requirement for the production of IFN-gamma by Th1 lymphocytes that mediate cellular immunity. In this study, we restored antigen-specific, cell-mediated immunity, delayed hypersensitivity, to ethanol-consuming C57BL/6 or BALB/c mice with a single 100 ng of intravenous injection of recombinant IL-12 at the time of immunization. The addition of exogenous recombinant IL-12 to co-cultures of antigen-presenting cells derived from ethanol-consuming mice and purified T cells derived from ethanol-nonconsuming DO11.10 repairs the ability of Th1 cells to make IFN-gamma in response to antigen. Administration of recombinant IL-12 opens a potential for restoring cell-mediated immune function to ethanol-consuming individuals.
Peterson
J D
JD
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611-3072, USA.
Vasquez
K
K
Waltenbaugh
C
C
D000437:Alcoholism / Q000276:immunology*; D000818:Animals; D005260:Female; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology; D007111:Immunity, Cellular / Q000187:drug effects* / Q000276:immunology; D007275:Injections, Intravenous; D018664:Interleukin-12 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000494:pharmacology
D011994:Recombinant Proteins; D018664:Interleukin-12