An Analysis of Acute Changes in Interleukin-6 Levels After Treatment of Hepatitis C with Consensus Interferon

Scott J. Cotler, K. Rajender Reddy, Jon McCone, Darin L. Wolfe, Anguo Liu, Teresa R. Craft, Mary W. Ferris, Andrew J. Conrad, Jeff Albrecht, Mary Morrissey, Daniel R. Ganger, Howard Rosenblate (+3 others)
2001 Journal of Interferon and Cytokine Research  
Cytokine production has been implicated in the antiviral response to interferon-a (IFN-a) in hepatitis C and in the development of IFN-a-related side effects. We characterized acute changes in serum cytokine levels following administration of a single dose of consensus IFN (IFN-con1) and during continuous treatment of chronic hepatitis C patients. Serum samples were collected at baseline, at multiple times early after IFN administration, and weekly thereafter. Viral RNA titers were assessed by
more » ... s were assessed by RT-PCR, and viral kinetics were followed. ELISA assays were used to measure IFN-g, tumor necrosis factor-a (TNF-a), interleukin-2 (IL-2), IL-4, IL-6, and IL-16. Serum cytokine levels were low at baseline. IL-6 was detected in patients with hepatitis C but not in healthy control subjects by either ELISA or RT-PCR, indicating that low levels of circulating IL-6 were associated with hepatitis C infection. None of the cytokines measured increased significantly after IFN administration except for IL-6. IL-6 levels rose rapidly, peaked at 6-15 h in a dose-dependent manner, and returned to baseline by 48 h in both patients receiving a single dose of IFN and those receiving continuous treatment. This was confirmed by RT-PCR. Pretreatment IL-6 levels were directly correlated with area under the curve (AUC) for IL-6 during the 24 h after IFN dosing (r 5 0.611, p 5 0.007). Viral titers decreased within 24-48 h after a single dose of IFN-con1. Changes in hepatitis C RNA titers were not significantly associated with pretreatment IL-6 levels or with changes in IL-6 levels. In conclusion, (1) baseline serum cytokine levels, except for IL-6, were low or within the normal range in patients with hepatitis C, (2) IL-6 levels were detected in some patients with hepatitis C before treatment but not in healthy controls, (3) IL-6 levels increased acutely after a single dose of IFN-a, and IL-6 induction was related to baseline IL-6 level, and (4) changes in IL-6 levels did not correlate with the early virologic response to IFN.
doi:10.1089/107999001317205132 pmid:11798458 fatcat:dxubustnkfdghbkxlbzfzzkgv4