Investigating the mechanisms underpinning antipsychotic-mediated pneumonia

Abstract

Background: The mechanisms behind the association between antipsychotics and pneumonia risk remain inadequately understood. Existing studies propose that antipsychotics might attenuate the immune response through cytokine modulation. The present study aimed to explore the impact of olanzapine and quetiapine on surface markers expression and cytokines released by CD4+ lymphocytes.

Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from four healthy volunteers. Olanzapine doses (6, 20, and 60 ng) and quetiapine doses (15, 50, 150 ng) were employed. The cells were stimulated with Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA). Stimulated cells were treated with olanzapine or quetiapine and compared to control cells. Flow cytometry was used to analyse CD25, CD28, CD127 (IL-7R-a), CD152 (CTLA4), CD274 (PD-L1), CD279 (PD-1) markers, and cytokines IL-2, IL-10, and IFN-Y. Statistical analyses were performed with GraphPad Prism 9.0, employing one way- analysis of variance (ANOVA) and Friedman tests (P < 0.05 for significance).

Results: Olanzapine and quetiapine increased CD25 expression, with olanzapine 20 ng reached statistical significance in PA-stimulated cells. PD-L1 expression exhibited an upward trend in SA-stimulated cells treated with both drugs, with quetiapine 15 ng being significant. Both drugs significantly increased CD28 expression in the stimulated cells. CD152 decreased slightly with therapeutic doses of both drugs in PA-stimulated cells. CD127 and PD-1 expressions remained unchanged. Regarding cytokines, olanzapine 6 ng significantly reduced IL-2 release in stimulated cells, while quetiapine caused a mild IL-2 release in PA-stimulated cells. IFN-Y release slightly dropped in PA-stimulated cells in both drugs. Quetiapine slightly lowered IFN-Y release in SA-stimulated cells, whereas olanzapine left IFN-Y unchanged. IL-10 release decreased significantly with olanzapine 6 ng and 20 ng in PA and SA-stimulated cells, and quetiapine led to a slight reduction in IL-10 release.

Conclusions: This in vitro study revealed how olanzapine and quetiapine affect CD4+ markers and cytokines. It emphasizes immune reduction via elevated CD25 and PD L-1 markers, known to decrease activated T-cells. Reduced immune response is evidenced by lower cytokine levels from activated T-cells, possibly increasing infection susceptibility, including pneumonia. Immune stimulation via CD28 and CD152 modulation might induce immunosuppression over time, exacerbating infection risk. Further studies are warranted to investigate the impact of antipsychotics on immune cells surface markers to better understand their immunomodulatory effects.