Differential effects of nicotine and aging on splenocyte proliferation andthe production of Th1-versus Th2-type cytokines

Nicotine has a multitude of biological actions in the central and periphera l nervous systems where nicotinic acetylcholine receptors are found. Nicoti nic acetylcholine receptors have also been identified on immune cells, but the effects of nicotine on immune responses are not well characterized. The se studies tested the hypotheses that nicotine has an effect on both T-lymp hocyte proliferation and the production of cytokines by activated T cells, processes that are necessary for effective T-cell-mediated immune responses . In addition, the effects of nicotine on these immune responses in aging a nimals and the effects of nicotine exposure prior to immunostimulation were investigated. Murine splenocytes were exposed to nicotine and stimulated w ith concanavalin A (ConA). The highest concentration of nicotine (128 mu g/ ml) significantly depressed proliferation of T cells both when nicotine and ConA were added concurrently and when nicotine was added 3 hr prior to Con A. Nicotine, added concurrently with ConA at concentrations between 0.25 an d 64 mu g/ml, significantly inhibited the production of IL-10 by splenocyte s from young adult mice, whereas the inhibition of production of IL-10 by s plenocytes from old mice was significantly inhibited, but the response was more variable, depending on the nicotine concentration. In contrast, the pr oduction of IFN-gamma by splenocytes from either young adult or old mice wa s not affected when nicotine (0.016-64 mu g/ml) was added concurrently with ConA. Pre-exposure to 1 mu g/ml of nicotine for 3 hr significantly enhance d the production of IFN-gamma by splenocytes from young adult mice, whereas pre-exposure to 0.016 mu g/ml of nicotine tended to but did not significan tly enhance IFN-gamma production. Nicotine is now being used as an over-the -counter drug by people who differ in age and general immunocompetence. The refore, the effects of nicotine on immune responses, independent from the e ffects of the other chemicals found in tobacco, need to be investigated.