An analysis of acute changes in interleukin-6 levels after treatment of hepatitis C with consensus interferon

J Interferon Cytokine Res. 2001 Dec;21(12):1011-9. doi: 10.1089/107999001317205132.


Cytokine production has been implicated in the antiviral response to interferon-alpha (IFN-alpha) in hepatitis C and in the development of IFN-alpha-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 RT-PCR, and viral kinetics were followed. ELISA assays were used to measure IFN-gamma, tumor necrosis factor-alpha (TNF-alpha), 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 = 0.611, p = 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-alpha, 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.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / therapeutic use*
  • Cytokines / blood
  • Hepacivirus / genetics
  • Hepacivirus / isolation & purification
  • Hepatitis C / drug therapy*
  • Hepatitis C / immunology*
  • Hepatitis C / virology
  • Humans
  • Interferon Type I / therapeutic use*
  • Interferon-alpha
  • Interleukin-6 / blood*
  • Interleukin-6 / genetics
  • Kinetics
  • Middle Aged
  • RNA, Messenger / biosynthesis
  • RNA, Viral / analysis
  • Recombinant Proteins


  • Antiviral Agents
  • Cytokines
  • Interferon Type I
  • Interferon-alpha
  • Interleukin-6
  • RNA, Messenger
  • RNA, Viral
  • Recombinant Proteins
  • interferon alfacon-1