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-kappaB) regulates the expression of cytokines. However, it remains unclear whether the interaction between NF-kappaB 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-1beta (IL-1beta) 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-1beta, TNF-alpha) and NF-kappaB were detected by using semiquantitative reverse transcription polymerase chain reaction (RT-PCR). NF-kappaB activation was examined by using transcription factor assay kits.
RESULTS: Schizophrenic patients showed significantly higher serum levels and PBMC mRNA expressions of IL-1beta 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-1beta in schizophrenic patients. NF-kappaB activation and PBMC mRNA expression in patients were significantly higher than those in healthy subjects. Furthermore, PBMC mRNA expressions of IL-1beta and TNF-alpha were positively correlated to NF-kappaB activation in both schizophrenic patients and healthy control subjects.
CONCLUSIONS: Schizophrenic patients showed activation of the cytokine system and immune disturbance. NF-kappaB activation may play a pivotal role in schizophrenia through interaction with cytokines.