Ethanol consumption in humans and in experimental animals has been shown to depress many specific immune functions. It has been hypothesized that the depressed immune response may contribute to the increased prevalence of infectious diseases and tumors in alcoholics. Studies suggest that chronic ethanol consumption depresses T-lymphocyte helper function. CD4 T- helper cells can be divided into two distinct phenotypic subsets acting through different lymphokine secretion patterns. Th1 cells give rise to cell-mediated immunity; Th2 are responsible for antibody-mediated immunity. Parasitic infections in mice provide the premier examples of infections controlled exclusively by either the Thl or the Th2 system. Two of these models have been thoroughly investigated, (a) Leishmania major, a protozoan infection, where immunity is totally Thl dependent and (b)Strongyloides stercoralis, a nematode infection, where immunity is totally Th2 dependent. The effect of ethanol consumption on the development of protective immunity to these infections will be determined, thereby elucidating the effect of ethanol on Thl and Th2 function. The objectives of this study are to (i) to determine the appropriate protocol for the administration of ethanol to mice for the demonstration of an effect on CD4 cell function (ii) to determine the effect of ethanol on protective immune responses dependent on either Thl or Th2 cells and (iii) to investigate the mechanism by which ethanol causes an alteration in the protective immune response. The results obtained with these two parasitic infection models will provide information on the effects of ethanol consumption on protective immunity dependent on CD4 cells.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AA011562-01
Application #
2384348
Study Section
Special Emphasis Panel (ZAA1-DD (01))
Project Start
1997-07-01
Project End
1999-06-30
Budget Start
1997-07-01
Budget End
1998-06-30
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Thomas Jefferson University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
061197161
City
Philadelphia
State
PA
Country
United States
Zip Code
19107
Krolewiecki, Alejandro; Leon, Shalom; Scott, Phillip et al. (2002) Activity of azithromycin against Leishmania major in vitro and in vivo. Am J Trop Med Hyg 67:273-7
Wang, C C; Nolan, T J; Schad, G A et al. (2001) Infection of mice with the helminth Strongyloides stercoralis suppresses pulmonary allergic responses to ovalbumin. Clin Exp Allergy 31:495-503
Krolewiecki, A J; Leon, S; Scott, P A et al. (2001) Effect of chronic ethanol consumption on protective T-helper 1 and T-helper 2 immune responses against the parasites Leishmania major and Strongyloides stercoralis in mice. Alcohol Clin Exp Res 25:571-8