IL-17 may mediate antipsychotic benefits in schizophrenia
MedWire News: Antipsychotic agents may act by increasing production of the cytokine interleukin (IL)-17, say German researchers, who add that the findings support the proposed involvement of the immune system in the pathophysiology of schizophrenia.
In addition to evidence from genetic studies suggesting that the major histocompatibility region is associated with schizophrenia, epidemiological, clinical, and preclinical findings indicate that exposure to infections may be an etiological factor in schizophrenia.
Noting that schizophrenia patients have altered levels of various cytokines in the blood and cerebrospinal fluid, Hubertus Himmerich, from the University of Leipzig, and colleagues stimulated whole blood samples, taken from ten healthy females, with toxic shock syndrome toxin 1(TSST-1).
The blood samples were supplemented with four different concentrations of the antipsychotics chlorpromazine, haloperidol, clozapine, N-desmethylclozapine, or quetiapine, or left unsupplemented. Levels of the cytokines IL-1β, IL-2, IL-4, IL-6, IL-17 and tumor necrosis factor (TNF)-α were then measured.
In unsupplemented blood, TSST-1 increased concentrations of all cytokines significantly. The presence of antipsychotics had no effect on IL-1β and IL-6 and variable effects on TNF-α and IL-2, with some drugs increasing and others decreasing levels.
Specifically, IL-2 levels were increased by chlorpromazine and decreased by N-desmethylclozapine and quetiapine, with a similar pattern observed for TNF-α, the team reports in the Journal of Psychiatric Research.
Three concentrations of chlorpromazine increased levels of IL-4 significantly, as did three concentrations of clozapine and N-desmethylclozapine. However, all concentrations of clozapine, N-desmethylclozapine, and quetiapine, and two concentrations of chlorpromazine and haloperidol, increased IL-17 levels significantly.
The team says: "The most intriguing finding of this study is the elevation of IL-17 by all tested antipsychotics." Therefore,"IL-17 elevation may be considered as a common trait of antipsychotic drugs."
They add: "In schizophrenia, a blunted type-1 immune response is reported… It could be the case that an induction of... IL-17, which induces the production of pro-inflammatory and type-1 cytokines, could counteract this blunted type-1 immune response."
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By Liam Davenport