Excessive alcohol consumption is a major threat to human health. Normal host defense mechanisms are compromised in alcoholic patients, often resulting in pronounced frequency and severity of infections. Both clinical and experimental evidence suggest that alcohol alters the immune system. Chronic alcohol consumption impairs induction of human cell- mediated immune responses and elevates serum antibody levels. Studies from our laboratory during the initial granting period for this ongoing project, show that ethanol has a twofold effect on the immune response; it enhances specific humoral immunity and impairs induction of specific cell- mediated immunity. More specifically, ethanol enhances poly(Glu5OTyr50) (GT)-specific humoral immunity and impairs poly(Glu6OAla3OTyr10)(GAT)- specific cell-mediated immunity regulated by CD4-bearing helper (Th) lymphocytes designated Th2 and Th1, respectively. Despite the importance of alcohol in compromising host defense, little is known of the mechanism(s) underlying ethanol-caused immune alteration. New findings from our laboratory strongly suggest that ethanol alters cytokine expression, resulting in profound alteration of immune function. We propose that alteration of cytokine expression by ethanol plays a critical role in the modification of specific immune responses by alcohol consuming individuals. We propose to direct the activities of our laboratory toward three major goals: 1) To further define the conditions and the extent whereby ethanol alters the immune function in inbred strains of mice. 2) To determine which cells of the immune system are affected by ethanol consumption, and 3) To determine the underlying mechanism(s) for ethanol's alteration of specific immune function. Our laboratory is now in a position to critically assess how alcohol alters immune function. Our data suggest that one of the mechanisms whereby alcohol alters immune function is by the up- or downregulation of cytokine expression. These experiments are designed to critically evaluate whether alcohol or its metabolites affect cytokine expression in a manner that favors one type of immune function over another. These studies are critical to the development of therapeutic strategies for alcoholic patients who are a risk to infectious disease.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA008275-08
Application #
2769138
Study Section
Special Emphasis Panel (ZRG4-ALTX-2 (01))
Project Start
1991-04-01
Project End
2002-08-31
Budget Start
1998-09-01
Budget End
1999-08-31
Support Year
8
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Microbiology/Immun/Virology
Type
Schools of Dentistry
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Ostrovidov, Serge; Howard, Laurence M; Ikeda, Masato et al. (2002) Restoration of ethanol-compromised T(h)1 responses by sodium orthovanadate. Int Immunol 14:1239-45
Alnadjim, Ziad; Kayali, Zeid; Haddad, Wael et al. (2002) Differential effects of T-cell activation on gastric and small bowel permeability in alcohol-consuming mice. Alcohol Clin Exp Res 26:1436-43
Latif, Omar; Peterson, Jeffrey D; Waltenbaugh, Carl (2002) Alcohol-mediated polarization of type 1 and type 2 immune responses. Front Biosci 7:a135-47
Wang, K; Busker-Mannie, A E; Hoeft, J et al. (2001) Prolonged Hya-disparate skin graft survival in ethanol-consuming mice: correlation with impaired delayed hypersensitivity. Alcohol Clin Exp Res 25:1542-8
Starkenburg, S; Munroe, M E; Waltenbaugh, C (2001) Early alteration in leukocyte populations and Th1/Th2 function in ethanol-consuming mice. Alcohol Clin Exp Res 25:1221-30
Waltenbaugh, C; Vasquez, K; Peterson, J D (1998) Alcohol consumption alters antigen-specific Th1 responses: mechanisms of deficit and repair. Alcohol Clin Exp Res 22:220S-223S
Peterson, J D; Herzenberg, L A; Vasquez, K et al. (1998) Glutathione levels in antigen-presenting cells modulate Th1 versus Th2 response patterns. Proc Natl Acad Sci U S A 95:3071-6
Waltenbaugh, C; Peterson, J D (1997) Ethanol impairs the induction of delayed hypersensitivity in C57BL/6 mice. Alcohol 14:149-53
Chang, W; Waltenbaugh, C; Borensztajn, J (1997) Fatty acid ethyl ester synthesis by the isolated perfused rat heart. Metabolism 46:926-9
Schodde, H; Hurst, S; Munroe, M et al. (1996) Ethanol ingestion inhibits cell-mediated immune responses of unprimed T-cell receptor transgenic mice. Alcohol Clin Exp Res 20:890-9

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