Predominance of type 1 (Th1) cytokine production in the liver of patients with HCV-associated mixed cryoglobulinemia vasculitis.
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.
Saadoun
David
D
Service de Médecine Interne, Hôpital Pitié-Salpêtrière, 47 bd de l'hôpital, 75013 Paris, France.
Boyer
Olivier
O
Trébeden-Nègre
Hélène
H
Limal
Nicolas
N
Bon-Durand
Véronique
V
Andreu
Marita
M
Klatzmann
David
D
Piette
Jean Charles
JC
Cacoub
Patrice
P
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*
D016207:Cytokines; D007476:Ionophores; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate