Suppressive effect of TRH and imipramine on human interferon-gamma and interleukin-10 production in vitro

It has been established that thyrotropin-releasing hormone (TRH) affects several aspects of immunoreactivity, e.g. production of pro-inflammatory cytokines, and enhances therapeutic efficiency of classic tricyclic antidepressants. On the other hand, it has been suggested that pro-inflammatory cytokines play a role in the etiology of depression, whereas the therapeutic efficacy of antidepressants is related to their negative immunoregulatory effect. In order to verify the hypothesis that the TRH-induced increase in the therapeutic efficiency of classic tricyclic antidepressants results from synergistic inhibitory effects of those two agents on the secretion of pro-inflammatory cytokines, we studied the effect of imipramine appliedjointly with TRH on the production of IFN-gamma and IL-10 by human whole blood cells stimulated in vitro by mitogens. A significant decrease in the production of IFN-gamma and IL-10 cytokines, by 36% and 34%, respectively, was observed in cells stimulated with mitogens and co-incubated with imipramine and TRH (either given at a dose of 10(-5) M). Under the same conditions, TRH alone did not change the production of those cytokines. Furthermore, imipramine alone decreased, not statistically significantly, though, the production of IFN-gamma. Hence our data only partly support the above-mentioned hypothesis, since TRH and imipramine applied jointly suppress the production of both the pro-inflammatory IFN-gamma and the anti-inflammatory IL-10 cytokines.