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.
Kubera
M
M
Department of Endocrinology, Polish Academy of Sciences, Kraków.
Kenis
G
G
Bosmans
E
E
Jaworska-Feil
L
L
Lasoń
W
W
Scharpe
S
S
Maes
M
M
D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007099:Imipramine / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000096:biosynthesis*; D008297:Male; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*
D000929:Antidepressive Agents, Tricyclic; D016753:Interleukin-10; D013973:Thyrotropin-Releasing Hormone; D007371:Interferon-gamma; D007099:Imipramine