This is an application for continuation of a study concerning marijuana and the immune response system. It is well known there is a public health risk of substance abuse including marijuana smoking in adults and juveniles. Many studies have shown that marijuana smoking may alter lymphocyte function. Studies in this laboratory, as well as in others, have also shown that administration of cannabinoid substances, including marijuana components, into animals modifies the biologic responsiveness of lymphocytes and macrophages. For example, we have shown that mice injected with THC, the major psychoactive component of marijuana, become deficient in production of a variety of cytokines including interferons, interleukins, etc., as well as cellular immune responses mediated by macrophage, NK cells, and CTLs, etc. We have also previously shown that addition of THC in vitro to lymphoid cells affects antibody formation, either enhancing or suppressing the response, and can also enhance or suppress proliferation of lymphocytes stimulated with T or B cell mitogens. Furthermore, we have also investigated the effects of THC on cellular immunity to the intracellular bacterium Legionella pneumophila and found that mice given this cannabinoid are more susceptible to infection and that cells involved in host resistance and immunity to Legionella, namely macrophages and T lymphocytes, are influenced by marijuana. We have also tested THC effects on freshly isolated as well as cloned T lymphocytes, NK cells and macrophages. Other studies have shown that THC depresses IL,2 production by T lymphocytes but IL-1 production is enhanced in macrophages. At the molecular level we have examined the effects of THC on IL,2 in terms of receptors for this lymphokine, the message for the receptors, and the genetic control of IL-2 formation. Thus we propose to continue this productive study for an additional period of time and continue to determine how THC, as well as its major psychoactive metabolite, i.e., 11-OH THC, affects immunity to an intracellular bacterium, i.e., Legionella, utilizing a variety of immunological approaches as well as continue to investigate the effects of and 11-OH THC in vitro on molecular mechanisms of macrophage and T cell function, i.e., production of interleukin 1 and 2 at the ene levels.
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