Previous studies in this laboratory examining the influence of marijuana components on immune function indicated that delta 9- THC and its metabolic product 11 OH-THC have, for the most part, inhibitory effects on a wide variety of immune functions. There is a strong belief that co-factors are involved in the acquired immunodeficiency syndrome (AIDS). Studies will be performed in this proposed investigation both in vivo and in vitro with cannabinoid treatment in a murine AIDS model. Extensive studies in previous years in this laboratory have shown that the murine retrovirus, Friend leukemia virus, causes a profound immunodepression in mice and this is equivalent to AIDs. We have shown that FLV infection markedly inhibits various cellular functions important in immune responses, including functions based upon T and B cells and macrophages. Soluble mediators of immunity, including interleukins and lymphokines, are also markedly affected by FLV infection in vivo and in vitro. Similarly, THC and other cannabinoids inhibit soluble mediator responses by lymphoid cells. THC also has dramatic effects on the function of B cells, T cells and macrophages. In the proposed studies, the effects of THC as a co-factor in AIDS will be examined in detail, using both in vivo and in vitro models. For the in vivo system, THC and other cannabinoids will be administered singly and in different doses to mice prior to, during, and following challenge infection with graded amounts of FLV to determine the effects of the cannabinoid in altering susceptibility to virus induced immunosuppression. The effects of THC on specific classes of immunocytes will be determined in vitro. THC is added directly to immunocompentent spleen cells and to distinct cell populations, including thymocytes, bone marrow cells and adherent cell populations rich in macrophages. The cells will be examined for susceptibility and/or resistance to FLV infection and their ability to produce lymphokines important in resistance to virus infection. The mechanism whereby THC alters susceptibility to FLV infection and enhances immunodeficiency will be examined by co-culture experiments and experiments dealing with treatment of different cell populations in vitro and in vivo with THC and determining whether these cells release mediators of immunity which affect other cells in regards to susceptibility to virus infection and immunosuppression. By means of these experiments it will be possible to ascertain whether THC and other marijuana components are indeed co- factors in enhancing leukemogenesis induced by FLV, possibly by increasing or affecting the ability of FLV to depress immunity. We believe it is important to determine whether or not cannabinoids have a synergistic effect on FLV induced immunosuppression and these experiments will further the goals of NIDA in investigating the effects of drugs of abuse as co- factors in acquired immunodeficiency syndrome.
