| Schizophrenia is a severe,chronic,neurodevelopmental mental health disorder with unclear molecular mechanisms.Altered immune function and inflammation are found in schizophrenia,suggesting that immune system may play a key role in its pathophysiology.Antipsychotic drugs(APDs)are used to treat schizophrenia and other psychiatric disorders.However,most of these drugs present side effects.Drug-induced neutropenia or agranulocytosis has been observed in patients treated with APDs.Neutrophils are one of the first lines of defense against invading microbes.When there is inflammation in the body,Neutrophils are recruited to the site of infection,effectively kill microorganisms by phagocytosis,degranulation,and generation of reactive oxygen species.In certain conditions,neutrophils enhance their antimicrobial properties by releasing neutrophil extracellular traps(NETs).Some studies report that APDs can regulate the function of T cells and macrophages.Neutrophil functions may also be regulated by APDs.At present,the mechanism of APDs’ effect on neutrophil function is not well characterized.In this study,we found that purified neutrophils treated in vitro with Antipsychotic drugs show enhanced potential of release neutrophil extracellular traps(NETs).Olanzapine,clozapine,aripiprazole and brexpiprazole increased the expression of human neutrophil proinflammatory cytokines IL-1α、IL-1β、IL-6、IFN-γ.Cariprazine increased the expression of human neutrophil proinflammatory cytokines IL-1α、IL-6.Risperidone increased the expression of human neutrophil proinflammatory cytokines IL-α 、 IL-6 、 TNF-α.At the same time,in vivo experiments showed that antipsychotic drugs increased the release of NETs near the liver and pancreas of mice.This study revealed a possible biological mechanism for the side effects of antipsychotics. |
