Serum tumour necrosis factor-α and transforming growth factor-β levels in chronic hepatitis C patients are immunomodulated by therapy

被引:45
作者
Neuman, MG
Benhamou, JP
Bourliere, M
Ibrahim, A
Malkiewicz, I
Asselah, T
Martinot-Peignoux, M
Shear, NH
Katz, GG
Akremi, R
Benali, S
Boyer, N
Lecomte, L
Le Breton, V
Le Guludec, G
Marcellin, P
机构
[1] Sunnybrook & Womens Coll, Hlth Sci Ctr, Div Clin Pharmacol, Toronto, ON M4N 3M5, Canada
[2] Univ Toronto, Dept Pharmacol, Toronto, ON, Canada
[3] Serv Hepatol, Clichy, France
[4] Hop Beaujon, Clichy, France
[5] St Joseph Hosp, Marseille, France
关键词
chronic hepatitis C; histological activity and fibrosis index; pegylated-interferon; transforming growth factor beta; tumour necrosis factor alpha;
D O I
10.1006/cyto.2001.0997
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Our aims were: (i) to characterize serum levels of tumour necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-0) in non-cirrhotics with hepatitis C; (ii) to correlate levels of theses cytokines with degree of disease at baseline; (iii) to characterize the imuno-modulatory effects of therapy with response and (iv) to compare profiles of cytokines in patients treated with pegylated-interferon alpha-2b monotherapy (PMT) vs its combination with ribavirin (PCT1-low dose ribavirin and PCT2-high dose ribavirin). We studied 56 patients that were part of two randomized, controlled, clinical trials. At baseline, high TNF-a levels paralleled the degree of inflammation as determined by histology. In PCT2, a significant reduction was seen in levels of TNF-alpha TGF-beta and fibrosis scores when comparing baseline with follow-up. In sustained responders, regardless of therapy, the histological activity scores were lower at follow-up as compared to baseline. In conclusion, PCT2 is able to constantly reduce and sustain TNF-alpha levels, which is responsible for the sustained decline in liver inflammation as shown by the histological activity index and it is also able to reduce fibrosis as judged both by TGF-beta levels and fibrosis scores.
引用
收藏
页码:108 / 117
页数:10
相关论文
共 33 条
[1]   An algorithm for the grading of activity in chronic hepatitis C [J].
Bedossa, P ;
Poynard, T .
HEPATOLOGY, 1996, 24 (02) :289-293
[2]   Different cytokine profiles of intrahepatic T cells in chronic hepatitis B and hepatitis C virus infections [J].
Bertoletti, A ;
DElios, MM ;
Boni, C ;
DeCarli, M ;
Zignego, AL ;
Durazzo, M ;
Missale, G ;
Penna, A ;
Fiaccadori, F ;
DelPrete, G ;
Ferrari, C .
GASTROENTEROLOGY, 1997, 112 (01) :193-199
[3]   Role of early cytokines, including alpha and beta interferons (IFN-α/β), in innate and adaptive immune responses to viral infections [J].
Biron, CA .
SEMINARS IN IMMUNOLOGY, 1998, 10 (05) :383-390
[4]  
Brown PMJ, 2001, CLIN BIOCHEM, V34, P167, DOI 10.1016/S0009-9120(01)00210-7
[5]  
DAVID M, 1995, MOL CELL BIOL, V15, P7050
[6]  
Fabris C, 1999, CLIN EXP IMMUNOL, V117, P556
[7]   Circulating Th1 and Th2 cytokines in patients with hepatitis C virus infection [J].
Fan, XG ;
Liu, WE ;
Li, CZ ;
Wang, ZC ;
Luo, LX ;
Tan, DM ;
Hu, GL ;
Zhang, Z .
MEDIATORS OF INFLAMMATION, 1998, 7 (04) :295-297
[8]   Pegylated interferon-α2b:: Pharmacokinetics, pharmacodynamics, safety, and preliminary efficacy data [J].
Glue, P ;
Fang, JWS ;
Rouzier-Panis, R ;
Raffanel, C ;
Sabo, R ;
Gupta, SK ;
Salfi, M ;
Jacobs, S .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 2000, 68 (05) :556-567
[9]   A dose-ranging study of pegylated interferon alfa-2b and ribavirin in chronic hepatitis C [J].
Glue, P ;
Rouzier-Panis, R ;
Raffanel, C ;
Sabo, R ;
Gupta, SK ;
Salfi, M ;
Jacobs, S ;
Clement, RP .
HEPATOLOGY, 2000, 32 (03) :647-653
[10]   Peginterferon alfa-2a in patients with chronic hepatitis C and cirrhosis [J].
Heathcote, EJ ;
Shiffman, ML ;
Cooksley, WGE ;
Dusheiko, GM ;
Lee, SS ;
Balart, L ;
Reindollar, R ;
Reddy, RK ;
Wright, TL ;
Lin, A ;
Hoffman, J ;
De Pamphilis, J .
NEW ENGLAND JOURNAL OF MEDICINE, 2000, 343 (23) :1673-1680