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

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. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.