In vivo and in vitro cocaine modulation on production of cytokines in C57BL/6 mice.

In the present study we used both in vivo and in vitro murine models to investigate the effects of cocaine on the release of cytokines (IL-1 alpha, IL-6, and TNF-alpha by peritoneal macrophages and splenocytes, IL-2, IL-4, IL-5, IL-10, and IFN-gamma produced by splenocytes. In vitro cocaine (0.1, 1, 10, 100 micrograms/ml) exposure inhibited all cytokines produced by ConA-stimulated spleen cells and LPS-stimulated macrophages in a concentration dependent manner. Different effects of cocaine administration on cytokine production were observed when female C57BL/6 mice were injected intraperitoneally with cocaine (40 mg/kg body weight for six weeks). Secretion of IL-2 by splenocytes was significantly enhanced by cocaine administration, whereas IFN-gamma was not affected. Secretion of IL-4 and IL-10 by splenocytes was significantly inhibited by cocaine administration, while secretion of IL-5 by splenocytes was significantly enhanced. Secretion of IL-6 and TNF-alpha by splenocytes was significantly enhanced by cocaine administration. Secretion of IL-6 by peritoneal macrophages was also significantly enhanced by the cocaine, while production of IL-1 alpha was not affected. However, release of TNF-alpha by peritoneal macrophages was significantly reduced by the cocaine administration. Therefore use of cocaine may alter the balance of cytokine production, and thereby adversely affects immune response and host defense.