Alcohol has a suppressive effect on both the cellular immune response and humoral immune response. Animals and humans who have ingested alcohol have a decrease in antibody response to new antigens. The mechanisms by which alcohol suppresses antibody formation are not known. The principal investigator will use an in vitro model of antibody formation to test the hypothesis that alcohol inhibits the antibody response by interfering with biochemical pathways responsible for initiating and sustaining the immune response in B and T lymphocytes. She will use the unique long term continuous non malignant cell lines of DNP specific B lymphocytes developed in her laboratory and KLH specific T helper lymphocytes to determine if alcohol directly effects both B and TH cells. These cell lines will then be used to determine which stage of B cell and T cell response is inhibited by alcohol. After determining the time in the immune response when suppression occurs, the same in vitro systems will be used to compare the changes in phosphotidyl inositol pathway, cyclic AMP levels and Ca+2 influx and mobilization which occur in the presence and absence of alcohol at the point of suppression. Phospholipid methylation and phosphorylation of a 44 Kd protein will also be examined if suppression appears to involve the action of B cell stimulation Factor 1 or B cell differentiation factor mu. Changes associated with suppression by acute alcohol exposure will then be compared to changes induced by chronic alcohol exposure. Chronic alcohol exposure will be accomplished both in vivo by feeding alcohol mice and using spleen cells, and in vitro by growing the cell lines in the presence of alcohol.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
7R01AA007519-03
Application #
3111252
Study Section
Alcohol Biomedical Research Review Committee (ALCB)
Project Start
1989-09-01
Project End
1990-08-31
Budget Start
1989-09-01
Budget End
1990-08-31
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Type
Schools of Medicine
DUNS #
005436803
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
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Aldo-Benson, M; Kluve-Beckerman, B; Hardwick, J et al. (1992) Ethanol inhibits production of messenger ribonucleic acid for kappa-chain in stimulated B lymphocytes. J Lab Clin Med 119:32-7
Aldo-Benson, M; Pratt, L (1991) Direct tolerance induction in mature B lymphocytes may resemble clonal anergy phenomenon. Immunol Res 10:79-88
Aldo-Benson, M; Borel, H; Scheiderer-Pratt, L et al. (1989) Immunologic tolerance to DNA in B cell lines from both normal and autoimmune mice. Immunol Res 8:263-70
Aldo-Benson, M (1989) Investigations of intrinsic abnormalities in DNA-specific B lymphocytes from autoimmune mice. J Autoimmun 2:269-82
Boguniewicz, M; Sunshine, G H; Borel, Y (1989) Role of the thymus in natural tolerance to an autologous protein antigen. J Exp Med 169:285-90
Aldo-Benson, M (1989) Mechanisms of alcohol-induced suppression of B-cell response. Alcohol Clin Exp Res 13:469-75