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UNIVERSITY OF ILLINOIS AT CHICAGO Department of Psychiatry Fifth Annual Research Forum – Extravaganza 2014 POSTER TITLE Altered gene expression of proinflammatory cytokines and their receptors in the lymphocyte of depressed patients DISEASE/KEY WORDS: biomarkers, proinflammatory cytokines, depression, major depressive disorder, lymphocytes, IL-1β, IL-6, TNF-α, IL-1R1, IL-1R2, IL-1RA, IL-6, Gp130, TNFR1, TNFR2 AUTHORS: H. ZHANG, H. S. RIZAVI, X. REN, G. N. PANDEY MENTEE CATEGORY: Postdoc Research Associate BACKGROUND: Abnormalities of the immune function have been implicated in the pathophysiology of depression. This is primarily based on the observation that treating cancer patients with a cytokine interferon(IFN)-α causes depressionlike symptoms and that protein levels of proinflammatory cytokines and their soluble receptors are increased in the serum of depressed patients. The soluble receptors are derived from proteolytic degradation of membranebound cytokine receptors, which are involved in signal transduction and mediate the functional and biological effects of cytokines. Although soluble cytokine receptors have been studied in depression, to our knowledge membrane-bound cytokine receptors were not studied in depression or other psychiatric disorders. METHODS: We determined the protein and mRNA expression of proinflammatory cytokines, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, and mRNA expression of their receptors IL-1R1, IL-1R2, IL-1R antagonist (IL1RA), IL-6R, glycoprotein (Gp)130, TNFR1, and TNFR2 in the lymphocytes from 26 drug-free, hospitalized MDD patients and 29 drug-free normal control (NC) subjects. The subjects were diagnosed according to DSM-IV criteria. Protein levels of cytokines were determined by ELISA, and mRNA levels of cytokines and cytokine receptors in lymphocytes were determined by the qPCR method. We found that the mean mRNA levels of the proinflammatory cytokines IL-1β, IL-6, and TNF-α were significantly increased in the lymphocytes of MDD patients compared with normal controls. The protein levels of the cytokines IL1β, IL-6, and TNF-α were also significantly increased in the plasma of MDD patients compared with normal controls. The mRNA levels of IL-1R1, IL-1RA, TNFR1, and TNFR2 were significantly increased in the lymphocytes of MDD RESULTS: RESEARCH MENTOR: Ghanshyam N. Pandey, Ph.D UNIVERSITY OF ILLINOIS AT CHICAGO Department of Psychiatry patients compared with normal controls. No significant differences were observed in mRNA levels of IL-1R2, IL-6R, or Gp130 between MDD patients and normal controls. CONCLUSIONS: These studies suggest that the reported abnormalities of cytokines and their soluble receptors observed in the plasma of MDD patients may be related to an abnormal gene expression of these cytokines and their receptors in the lymphocytes of MDD patients, and that their mRNA expression levels in the lymphocytes could be a useful biomarker for depression. To our knowledge, this is the first study of cytokine receptors in depressed patients.