Xylazine, an alpha(2)-adrenergic agonist, modulates proliferation of rat thymocytes in vivo and in vitro

The effect of xylazine, an alpha (2)-adrenergic agonist, on proliferation o f rat thymocytes in vivo and in vitro was examined. It was found that the a gonist administered to rats in vivo at doses of 2.5 mg/kg and 5 mg/kg stimu lated thymocyte proliferation to suboptimal (0.625 mug/ml) concentrations o f concanavalin A (Con A). A similar effect was confirmed in vitro when lowe r concentrations of xylazine (5 muM) were added to cultures of thymic cells from intact animals in the presence of both suboptimal and optimal (2.5 mu g/ml) Con A concentrations. Higher doses in vivo (25 mg/kg) and in vitro (5 0 muM, 100 muM and 250 muM) significantly inhibited proliferation of thymoc ytes to Con A. The phenomenon was followed by a decrease in interleukin-2 ( IL-2) production (in vivo and in vitro) and down-regulation of IL-2 recepto r alpha (IL-2R alpha) expression (in vitro). The exogenous IL-2 completely restored the inhibitory effect of xylazine in vivo was observed. Stimulator y effect of xylazine on proliferation of thymocytes was probably mediated t hrough alpha (2)-adrenoreceptors since it was blocked by yohimbine, an alph a (2)-adrenoreceptor antagonist. It seems that the pathways involved in inh ibition of thymocyte proliferation by xylazine are more complex because the xylazine-suppressed thymocyte proliferation was potentiated by yohimine. ( C) 2000 Prous Science. All rights reserved.