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 bipolar (BP) patients. 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 BP patients. Methods: We determined protein and mRNA expression of proinflammatory cytokines, and mRNA expression of their receptors in the lymphocytes from 29 drug-free, hospitalized BP patients and 30 drug-free normal control subjects. The subjects were diagnosed according to DSM-IV criteria. Plasma protein levels of cytokines were determined by ELISA; mRNA levels in lymphocytes were determined by the qPCR method. Results: We found that mean mRNA levels of proinflammatory cytokines IL-1β, IL-6, TNF-α, their receptors, TNFR1, IL-1R1, and the antagonist IL-1RA were significantly higher in the lymphocytes of BP patients 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 illness and that the mRNA levels of these receptors could be a potential biomarker.