Nicotine modulation of anti-viral immunity in periadolescent male and female C57BL/6J mice.

摘要

The link between tobacco use and poor health outcomes was clearly outlined in the 1964 Surgeon General's report (United States Department of Health, Education, and Welfare, 1964). However, the causal relationship between nicotine, the addictive component in tobacco, and its effects on immune function was not examined until the 1990's. Immune cells have been exposed to nicotine via in vitro and in vivo designs. However, the suppression of T- and B-lymphocytes, dendritic cell, macrophage, and neutrophil functioning by nicotine has only been observed using in vitro immune stimulation (e.g., concanavalin A or lipopolysaccharide exposure). Although valuable, these in vitro immune stimulation designs provide only a partial picture of the overall in vivo immune cell functioning.;This dissertation sought to understand how nicotine modulates the anti-viral immune response of male and female periadolescent C57BL/6J mice to herpes simplex virus (HSV)-1 infection. For seven days, male (n=59) and female (n=58) C57BL/6J mice were exposed to nicotine-spiked water at one of three concentrations (0 microg/mL, 50 microg/mL, and 200 microg/mL). On day 8, all mice were infected with HSV-1 in both rear foot pads. Nicotine exposure continued until day 12, when mice were sacrificed and popliteal lymph nodes were removed to observe the effects of nicotine on the HSV-1 anti-viral response (i.e., number of lymphocytes isolated, lymphocyte production of interferon (IFN)-gamma, HSV-1 specific T-lymphocyte lysis).;Females exhibited a greater anti-viral response (e.g., number of lymphocytes isolated and lymphocyte production of IFN-gamma) to HSV-1 compared to their male counterparts. In addition, the 50 microg/mL nicotine exposure group had a reduction in IFN-gamma production compared to the control group, which suggests a reduction in T-lymphocyte activation. However, there were no sex or nicotine treatment group differences in HSV-1 specific immunity. Therefore, the in vivo viral challenge resulted in a robust HSV-1 anti-viral response that was difficult to modulate with nicotine exposure in the present study. A discussion of the results and suggestions for future studies are presented.