Second generation atypical antipsychotics olanzapine and aripiprazole reduce expression and secretion of inflammatory cytokines in human immune cells

Schizophrenia and major depression are associated with alterations in peripheral inflammatory markers, and anti-inflammatory therapy has been proposed as a promising add-on approach in the pharmacologic treatment of both disorders. Second-generation atypical antipsychotics are currently first-line drugs in the treatment of schizophrenia and are also used as augmentation strategies in treatment-resistant major depression. Furthermore, these drugs have been reported to exhibit distinct metabolic side effects and to influence inflammatory processes. In this study, we used ex vivo stimulation of primary human peripheral blood mononuclear cells (PBMC) from healthy blood donors with atypical antipsychotics olanzapine or aripiprazole to examine effects on cytokine production independent from metabolic side effects and disease status. Both olanzapine and aripiprazole stimulation decreased mRNA levels of IL-1 beta, IL-6, and TNF-alpha and resulted in diminished protein concentrations of IL-6 and TNF-alpha in conditioned medium of stimulated PBMC. A multiplex approach revealed additional downregulation of IL-2; MIP-1 beta and IP-10 secretion. Similarly, olanzapine and aripiprazole stimulation of the human monocytic cell line THP-1 resulted in a significant decrease in expression and secretion of IL-1 beta and TNF-alpha. Our results suggest that atypical antipsychotics directly influence immune cell function and thereby highlight the importance to factor in potential side effects of drugs routinely used in treatment of schizophrenia and major depression on inflammatory processes when considering anti-inflammatory drug therapy as an additional treatment option.