Predominance of type 1 (Th1) cytokine production in the liver of patients with HCV-associated mixed cryoglobulinemia vasculitis

J Hepatol. 2004 Dec;41(6):1031-7. doi: 10.1016/j.jhep.2004.08.011.

Abstract

Background/aims: Patients with hepatitis C virus (HCV) mixed cryoglobulinemia (MC) vasculitis have a higher mortality rate and more frequent incidence of cirrhosis than their cryoglobulin-negative counterparts. To compare the cytokine profile of liver-infiltrating T cells in HCV-infected patients with or without MC vasculitis.

Methods: Hepatic biopsy specimens were obtained from HCV infected patients with and without MC vasculitis. Using intracellular staining and flow cytometry, we assessed the ability of freshly isolated liver T cells from these biopsies to produce IFN-gamma, TNF-alpha, IL-2, IL-4, and IL-10 in response to stimulation with PMA and ionomycin.

Results: HCV-MC vasculitis patients compared to HCV-MC negative controls have an enhanced hepatic T cells production of Th1-type cytokines [i.e. TNF-alpha(30.3 +/- 13% vs. 15.5 +/- 5%, P = 0.01), IL-2 (20.2 +/- 9% vs. 10 +/- 4%, P = 0.01) and IFN-gamma (22.2 +/- 11% vs. 9.4 +/- 4%, P = 0.008)], whereas IL-10, a representative Th2-type cytokine, was significantly lower (7.2 +/- 4% vs. 17 +/- 7%, P = 0.01).

Conclusions: T cell from the liver of HCV-MC vasculitis patients display a significantly augmented liver Th1 profile compared to MC-negative controls. This enhanced production of type-1 cytokines may account for a more severe course of liver disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Arthralgia / virology
  • Asthenia / virology
  • Case-Control Studies
  • Cryoglobulinemia / virology*
  • Cytokines / biosynthesis*
  • Female
  • Hepatitis C / complications*
  • Hepatitis C / metabolism
  • Hepatitis C / pathology
  • Humans
  • Ionomycin / pharmacology
  • Ionophores / pharmacology
  • Liver / metabolism*
  • Liver / pathology
  • Male
  • Middle Aged
  • Purpura / virology
  • Syndrome
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology
  • Tetradecanoylphorbol Acetate / pharmacology
  • Th1 Cells / metabolism*
  • Th1 Cells / pathology
  • Vasculitis / virology*

Substances

  • Cytokines
  • Ionophores
  • Ionomycin
  • Tetradecanoylphorbol Acetate