title: Multiplex cytokine profiling of initial therapeutic response in patients with chronic hepatitis C virus infection.
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-1beta 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.
authors.affiliation: Nazhi Zuhdi Transplant Institute, Integris Baptist Medical Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
authors.forename: Harlan
authors.initials: H
authors.lastname: Wright
authors.forename: Philip
authors.initials: P
authors.lastname: Alex
authors.forename: Thuan
authors.initials: T
authors.lastname: Nguyen
authors.forename: Teddy
authors.initials: T
authors.lastname: Bader
authors.forename: Ahmet
authors.initials: A
authors.lastname: Gurakar
authors.forename: Anthony
authors.initials: A
authors.lastname: Sebastian
authors.forename: Liberty
authors.initials: L
authors.lastname: Gonzales
authors.forename: Gemma
authors.initials: G
authors.lastname: Wallis
authors.forename: Mark
authors.initials: M
authors.lastname: Naylor
authors.forename: Igor
authors.initials: I
authors.lastname: Dozmorov
authors.forename: Michael
authors.initials: M
authors.lastname: Centola
authors.forename: Bakr
authors.initials: B
authors.lastname: Nour
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D016000:Cluster Analysis; D016207:Cytokines / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols; D011446:Prospective Studies; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b