Cocaine and Immunocompetence: Possible Role of Reactive Metabolites

Abstract

Although drug abuse has been widely discussed as a possible co-factor in the onset and/or progression of AIDS, available literature is not consistent with cocaine use being associated with marked effects on immunocompetence. The initial objective of the present investigation was to determine the effects of cocaine on immunocompetence following direct addition to cultured splenocytes from female B6C3F1 mice. Because cocaine is a potent local anesthetic, we used procaine as a comparative control in these studies. As discussed below, the results from these studies were not consistent with a role by direct immunomodulatory actions of cocaine. We speculated that the in vivo effects of cocaine on the immune system may be an indirect consequence of exposure. The overall purpose of this study was to begin to examine possible indirect mechanism(s) for the effects of cocaine on the immune system, with an emphasis on a role by reactive metabolites. Cocaine is metabolized to norcocaine and, ultimately to more reactive intermediates, via a minor metabolic pathway mediated by the cytochrome P-450 system. The generation of these metabolites is associated with hepatotoxicity, which is both sex- and strain-dependent (i.e., dependent on the relative activity of the P-450 system). To provide evidence for a role by P-450-dependent metabolites in cocaine’s actions on the immune system, we have compared the effects of subchronic (14 day) exposure to cocaine on the T-dependent antibody response in female B6C3F1 mice, female DBA/2 mice and male B6C3F1 mice.