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Effect of antipsychotics on microglia in vitro
Peripheral paradigms show that certain antipsychotics modulate secretion of cytokines and soluble cytokine-receptors, and it was suggested that this immunomodulation is involved in the mechanism of action (1,2). Microglia, originating from the same source as peripheral blood monocytes, might be the major CNS target. Thus, we investigated the effect of haloperidol and clozapine on the secretion of TNF-alpha, sTNFR’s and IL-6 as well as on cell death in vitro in microglial cell lines hypothesizing a differential modulation by these antipsychotics.
Two microglial cell lines were set up with/without lipopolysaccharide and combined with dilution series of clozapine or haloperidol. MTT assay and commercial ELISA in supernatants were applied.
Preliminary results support that clozapine unlike haloperidol significantly modulates secretion of sTNFR-p75 and TNF-alpha. If CNS born cells respond differentially to antipsychotics by modulating cytokine-secretion this will further support the hypothesis that immunomodulation is a mechanism of action of these drugs.
Hinze-Selch D, Pollmächer T. BrainBehavImmun 2001;15:282–318
Pollmächer T et al. JPsychiatrRes 2000;34:369–382
This study is supported by the Stanley Medical Research Institute.