Abnormal gene expression of proinflammatory cytokines and their receptors in the lymphocytes of patients with bipolar disorder.

OBJECTIVES

Abnormalities of protein levels of proinflammatory cytokines and their soluble receptors have been reported in plasma of patients with bipolar disorder (BP). In this study, we tested the hypothesis that the mRNA expression of membrane-bound receptors for proinflammatory cytokines will be altered in the lymphocytes of patients with BP.

METHODS

We determined protein and mRNA expression of proinflammatory cytokines, and mRNA expression of their receptors in the lymphocytes from 29 drug-free, hospitalized patients with BP and 30 drug-free normal control subjects. The subjects were diagnosed according to DSM-IV criteria. Plasma protein levels of cytokines were determined by enzyme-linked immunosorbent assay (ELISA); mRNA levels in lymphocytes were determined by the quantitative polymerase chain reaction (qPCR) method.

RESULTS

We found that mean mRNA levels of the proinflammatory cytokines interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α, and their receptors TNFR1, IL-1R1, and the antagonist IL-1RA were significantly higher in the lymphocytes of patients with BP compared with normal controls.

CONCLUSIONS

This study suggests that the observed abnormalities of membrane-bound cytokine receptors may alter the functional response of cytokines in BP and that the mRNA levels of these receptors could be a potential biomarker.