Investigation of serum cytokine levels and cytokine production in whole blood cultures of paranoid schizophrenic patients.

There is some evidence that the pathophysiology of schizophrenia is related to changes in the innate and adaptive immune systems. In an attempt to define a potential immunological dysfunction in schizophrenia, we measured the serum levels of several cytokines in the sera of 24 patients with paranoid schizophrenia and investigated the cytokine production in whole blood assays after stimulation in vitro with virus (Newcastle disease), phytohemagglutinin (PHA) or bacterial lipopolysaccharide (LPS) and compared them with healthy, normal controls. A significant increase of interleukin 6 (IL-6), IL-8 and interferon gamma (IFN-gamma) levels, but a decreased L-10 level were observed in the sera of patients with schizophrenia. No significant changes in the serum levels of IL-2, IL-4, IFN-alpha and tumor necrosis factor alpha (TNF-alpha) were detected in these patients. When cytokine production in vitro was examined, a significant defect in PHA-induced IL-2, L-4 and IFN-gamma, and in virus-induced IFN-alpha production, but no significant alterations in LPS-induced IL-6, IL- 10 and TNF-alpha production were observed. In summary, increased serum levels of some cytokines such as IL-6, IL-8 and IFN-gamma indicate an activation of the inflammatory response in schizophrenia, while the in vitro assay indicates significant changes in the Th1 (decreased production of 1L-2 and IFN-gamma) and Th2 (decreased production of IL-4) cell system responses. The role of the defective EFN-alpha production in the regulation of the imbalance between Th1 and Th2 cell system responses is suggested.