Substantial evidence demonstrates the presence of an inflammatory syndrome in schizophrenia, which is manifested by increased peripheral levels of interleukin-6 (IL-6), soluble interleukin-2 receptor (sIL-2R), and interleukin-1 receptor antagonist (IL-1RA). Unfortunately, the immunomodulatory effects of antipsychotics on peripheral cytokine levels remain poorly understood. Objectives: The objectives of the current systematic review are to determine if antipsychotics have anti-inflammatory

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... s in patients with schizophrenia-spectrum disorders and to examine the relationships between antipsychotic-induced cytokine changes and drug response or common side effects. Method: A systematic search was performed in the electronic databases PubMed and EMBASE. Results: We identified 39 studies measureing the effects of 8 antipsychotics on 13 inflammatory mediators and 4 cytokine receptors. This literature suggests that antipsychotics (especially clozapine) consistently decrease peripheral interleukin-2 (IL-2) levels and increase sIL-2R and soluble tumor-necrosis factor (sTNF-R) receptor levels. Changes in IL-2/sIL-2R levels seem to correlate with changes in positive symptoms. Preliminary results suggest that antipsychotics decrease interferon-γ (IFN-γ) and transforming growth factor-β (TGF-β) levels, and increase interleukin-4 (IL-4) levels. Antipsychotic-induced changes in IL-6, C-reactive protein (CRP) and tumor-necrosis factor-α (TNF-α) have been linked with common antipsychotic side effects (metabolic, fever). Discussion: Despite significant clinical heterogeneity across studies, this review has evidenced that antipsychotics can produce both anti-and pro-inflammatory effects that may partially contribute to drug response and druginduced side effects. In the future, a better under-standing of the molecular mechanisms of action of antipsychotics on inflammatory mediators will help to identify novel therapeutic strategies as well as novel biomarkers of treatment response and of drug-induced side effects in schizophrenia. * Corresponding authors. OPEN ACCESS V. Tourjman et al. / Advances in Bioscience and Biotechnology 3 (2012) 551-565 552 A total of 39 studies were identified that fulfilled our inclusion criteria [8, 9, 13, [18] [19] [20] [21] . These studies measured the effects of 8 antipsychotics (aripiprazole, clozapine, haloperidol, olanzapine, perphenazine, quetiapine, risperidone, and ziprasidone) on 13 inflammatory Head-to-head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia: A systematic review and meta-analysis. Schizophrenia Research, 23, 225-233.