Effect of aripiprazole on cytokine production by T cells in schizophrenia

Objective. To evaluate the modulatory effect of the antipsychotic agent aripiprazole on ex vivo production of the cytokines interleukin-17 (IL-17) and interferon-γ (IFN-γ) by T-lymphocytes in patients with schizophrenia. Material and methods. The study included 15 patients diagnosed with schizophrenia and 12 healthy donors as the control group. A peripheral blood mononuclear cell (PBMC) model was employed to assess the effects of aripiprazole on cytokine profiles. Cells were stimulated with microparticles coated with antibodies to CD3 and CD28 surface markers. To investigate the roles of D1 and D2 dopamine receptors (D1DR and D2DR) in the mechanism of action of aripiprazole, PBMCs were stimulated in the presence of aripiprazole alone and in combination with specific antagonists: SCH23390 for D1DR and sulpiride for D2DR. Concentrations of IL-17 and IFN-γ in culture supernatants were measured using an enzyme-linked immunosorbent assay. Results. In patients with schizophrenia, the induced production of both IL-17 and IFN-γ by PBMC was significantly lower than in the healthy donor group. Aripiprazole exhibited a dose-dependent suppressive effect on cytokine secretion in both groups. Blockade of D1DR enhanced the inhibitory effect of aripiprazole, whereas blockade of D2DR diminished it. Isolated blockade of D1DR, in the absence of aripiprazole, inhibited cytokine production by stimulated PBMCs in both groups, while isolated blockade of D2DR had no significant effect. Conclusion. Aripiprazole may exert anti-inflammatory effects in schizophrenia by inhibiting the secretion of pro-inflammatory cytokines by T cells. This effect is likely mediated through D2DR activation.