The Interaction of Nuclear Factor-Kappa B and Cytokines Is Associated with Schizophrenia

Background: Many reports suggest that schizophrenia is associated with the inflammatory response mediated by cytokines, and nuclear factor-kappa B (NF-kappa B) regulates the expression of cytokines. However, it remains unclear whether the interaction between NF-kappa B and cytokines is implicated in schizophrenia and whether the effect of neuroleptics treatment for 4 weeks is associated with the alteration of cytokines. Methods: Sixty-five healthy subjects and 83 first-episode schizophrenic patients who met DSM-IV criteria and who were never treated with neuroleptics previously were included. Serum levels of cytokines such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) were examined by using sandwich enzyme immunoassay (EIA). Peripheral blood mononuclear cell (PBMC) mRNA expressions of cytokines (IL-1 beta, TNF-alpha) and NF-kappa B were detected by using semiquantitative reverse transcription polymerase chain reaction (RT-PCR). NF-kappa B activation was examined by using transcription factor assay kits. Results: Schizophrenic patients showed significantly higher serum levels and PBMC mRNA expressions of IL-1 beta and TNF-alpha compared with healthy subjects. However, treatment with the neuroleptic risperidone for 4 weeks significantly decreased serum levels and PBMC mRNA expressions of IL-1 beta in schizophrenic patients. NF-kappa B activation and PBMC mRNA expression in patients were significantly higher than those in healthy subjects. Furthermore, PBMC mRNA expressions of IL-1 beta and TNF-alpha were positively correlated to NF-kappa B activation in both schizophrenic patients and healthy control subjects. Conclusions: Schizophrenic patients showed activation of the cytokine system and immune disturbance. NF-kappa B activation may play a pivotal role in schizophrenia through interaction with cytokines.