Abstract
BACKGROUND: Cocaine affects not only the central nervous system, but also systemic immunity. The role of cocaine in gut mucosal integrity is not fully understood. METHODS: Here we evaluated the effect of cocaine use on gut endothelial permeability and system inflammation in rats that self-administered cocaine or saline and in humans using immunohistochemistry, qPCR, ELISA, and Transepithelial/transendothelial electrical resistance (TEER). RESULTS: Cocaine administration maintained intact and undisturbed intestinal mucosal structures, increased tight junction claudin 1 and 2 mRNA expression, and decreased plasma TNF-α levels, compared to the control group, at the end of study in rats. Further, cocaine treatment decreased gut endothelial permeability in a dose-dependent manner in human epithelial Caco-2 cells in vitro. Consistently, chronic cocaine users exhibited decreased plasma levels of TNF-α compared with non-drug users in vivo. However, plasma IL-6 levels were similar between cocaine use and control groups both in humans and rats in vivo. CONCLUSIONS: Our results from both human and rat studies in vivo and in vitro suggest that cocaine use may exert a protective effect on the integrity of gut mucosa and suppresses plasma TNF-α levels. This study may provide information on some beneficial effects of cocaine use on gut endothelial cells integrity and systemic inflammation.