The effects of alcohol on the immune system have been debated for many years. On one hand a small amount probably has no effect or possibly even a beneficial effect, but excessive amounts lead to increased infections. It may be an obvious connection that too much of anything will lead to health problems, but what is the mechanism involved? Will knowing this mechanism teach us anything about how the immune system works?
I was in a lab that wanted to find this out, and my work led to a paper in 2007. In summary we found that our mouse model for chronic alcohol abuse compromises the Th1 driven delayed type hypersensitivity reaction. The cell population we found to be responsible were a subpopulation of dendritic cells that were CD11c+CD8α+ which were impaired in their ability to activate Th1 cells. This is predicted to be due to glutathione depletion and resulting oxidative stress.
Since I have shifted my interest to cancer, I was curious as to what has been done since 2007 regarding the effects alcohol has on adaptive immunity. I was surprised to find a recent paper that cited my work. What Porretta et al did was look for the impact of alcohol on BCG-Induced Immunity Against M. Tuberculosis.
Tuberculosis is one of the many known infections that alcoholics have a greater change of succumbing to. The infection can either remain in a latent state (held at bay by the Th1 response) or through several mechanisms become active. Alcoholism can be a factor in driving the infection to the active state. Using the same mouse model as we used for studying the alcoholic’s immune system, they vaccinated mice with BCG, a live vaccine of the attenuated strain and followed up with pulmonary challenge. They found that alcohol consumption prior to vaccination impaired the ability of the vaccine to protect the mice from infection, but that alcohol consumption after vaccination produced had no effect on the effectiveness of the vaccine.
Since BCC is not effective in producing the Th1 and CTL immunity essential to recover from tuberculosis, and therefore not a popular vaccine in America. New vaccines are being developed and tested in the developing world where the cases of TB are higher. Since alcoholism is also high in developing countries, the current trials need to conducted without the added variable of alcohol.
Porretta et al (2011) The Impact of Alcohol on BG-Induced Immunity Against Mycobacterium tuberculosis. Alcohol Clin Exp Res 35:1530-1538.
Heinz R, Waltenbaugh C (2007) Ethanol consumption modifies dendritic cell antigen presentation in mice. Alcohol Clin Exp Res 31:1759–1771.
This is interesting so I did a general search on DCs and alcoholism and saw this study where they looked at mice and alcohol. They found that the DCs of mice who had been fed alcohol had both decreased antigen presentation and decreased cytokine production- and also (as one would suspect) lower T cell activation. It makes sense that alcoholics are more susceptible to a variety of infections!
ReplyDeleteA. Eden, V. Ortiz, and J.R. Wands, 2011. Ethanol inhibits antigen presentation by dendritic cells. Clin. Vaccine Immunol. 18:1157-1166