Abstract
Currently available prognostic tools are inadequate to discern the molecular basis of the heterogenic response in hepatitis C virus (HCV)-infected patients treated with the current standard of therapy. The expression and biological function of immune mediators have been shown to be critical in all phases of the immune response to HCV infection and likely therefore influence host response. Herein, a biometric multiplex serum cytokine assay was utilized to characterize the immunomodulatory effects of host response in 10 HCV patients. Serum levels of 17 cytokines were compared before and after 1 month of treatment and against controls. Overall serum cytokine levels were significantly higher in patients (P < 0.05) than controls. Additionally, viral titers decreased in all patients after 1 month of therapy, as did overall serum cytokine levels in the cohort (P < 0.05). To assess relationships between changes in cytokine levels and changes in viral titer, the cohort was divided into three statistically distinct subgroups based on changes in viral titers. Specific sets of cytokines decreased in each group: decreases in CCL4, interleukin (IL)-2, CXCL8, and IL-1β correlated with the greatest drops in viral titer, decreases in IL-5, granulocyte colony stimulating factor (G-CSF), and CCL4 correlated with moderate drops in viral titer, and only CCL2 correlated with the lowest drops in viral titer. Interestingly, decreases in CCL4 levels correlated with decreases in viral titers in all patients. CCL4 controls leukocyte influx and thus propagates inflammation. In conclusion, these data raise the possibility that characteristic changes in host response modulate the therapeutic response, demonstrating the prognostic power of serum cytokine profiling in chronic HCV.
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This publication was made possible by grants from Joullian Foundation, Kerr McGee Corporation, Dr. Henry Freeds Foundation, Samuel Roberts Noble Foundation, and E. L. & Thelma Gaylord Foundation and Grants P20 RR 017703, R21-AR-48378, NIH 1 P20 RR15577, and NIH 1 P20 RR16478 from the National Institutes of Health.
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Wright, H., Alex, P., Nguyen, T. et al. Multiplex Cytokine Profiling of Initial Therapeutic Response in Patients with Chronic Hepatitis C Virus Infection. Dig Dis Sci 50, 1793–1803 (2005). https://doi.org/10.1007/s10620-005-2940-y
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DOI: https://doi.org/10.1007/s10620-005-2940-y