title: Predominance of type 1 (Th1) cytokine production in the liver of patients with HCV-associated mixed cryoglobulinemia vasculitis.
abstract: OBJECTIVE
  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.
authors.affiliation: Service de Médecine Interne, Hôpital Pitié-Salpêtrière, 47 bd de l'hôpital, 75013 Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Saadoun
authors.forename: Olivier
authors.initials: O
authors.lastname: Boyer
authors.forename: Hélène
authors.initials: H
authors.lastname: Trébeden-Nègre
authors.forename: Nicolas
authors.initials: N
authors.lastname: Limal
authors.forename: Véronique
authors.initials: V
authors.lastname: Bon-Durand
authors.forename: Marita
authors.initials: M
authors.lastname: Andreu
authors.forename: David
authors.initials: D
authors.lastname: Klatzmann
authors.forename: Jean Charles
authors.initials: JC
authors.lastname: Piette
authors.forename: Patrice
authors.initials: P
authors.lastname: Cacoub
mesh_terms: D000328:Adult; D000368:Aged; D018771:Arthralgia / Q000821:virology; D001247:Asthenia / Q000821:virology; D016022:Case-Control Studies; D003449:Cryoglobulinemia / Q000821:virology*; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006526:Hepatitis C / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011693:Purpura / Q000821:virology; D013577:Syndrome; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018417:Th1 Cells / Q000378:metabolism* / Q000473:pathology; D014657:Vasculitis / Q000821:virology*
chemical_list: D016207:Cytokines; D007476:Ionophores; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate