Expression of the chemokine IP-10 correlates with the accumulation of hepatic IFN-γ and IL-18 mRNA in chronic hepatitis C but not in hepatitis B

被引:68
作者
Mihm, S
Schweyer, S
Ramadori, G
机构
[1] Univ Gottingen, Zentrum Innere Med, Abt Gastroenterol & Endokrinol, Div Gastroenterol & Endocrinol,Dept Internal Med, D-35075 Gottingen, Germany
[2] Univ Gottingen, Dept Pathol, Div Pathol, D-35075 Gottingen, Germany
关键词
hepatitis C virus (HCV); hepatitis B virus (HBV); interferon gamma (IFN-gamma); interferon gamma inducible protein 10 (IP-10; CXCL10); interleukin-18 (IL-18);
D O I
10.1002/jmv.10431
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The pathogenesis of hepatitis C virus-induced chronic liver disease is still poorly understood. Previous studies revealed enhanced hepatic expression of the Th1 prototype cytokine IFN-gamma in individuals with chronic hepatitis C. In accordance with several animal models of experimentally induced hepatitis, a Th1 lymphocyte driven inflammatory process, which involves newly infiltrated as well as resident monocytes/macrophages, has been proposed. An involvement of the interferon-gamma-inducible chemokine IP-10, which is chemoattractive for stimulated Th1 cells and monocytes, is also suggested. Using an HBV transgenic mouse model, a reduction of hepatic infiltration and liver disease was achieved recently by administration of antibodies directed against the interferon-gamma-inducible chemokine Mig and against IP-10. In the present study, expression of IP-10 was investigated both in serum and in the liver of patients with chronic hepatitis C and hepatitis B. Patients with liver diseases of non-viral etiologies served as controls. IP-10 expression was highest in hepatitis C. In chronic hepatitis C, but not in chronic hepatitis B nor in liver disorders unrelated to viral infections, IP-10 expression was strongly correlated with the amount of transcripts for IFN-gamma and to the amount of transcripts for the constitutively expressed macrophage derived cytokine IL-18. Hepatic inflammatory activity, however, was found to be associated more closely with IFN-gamma than with IP-10 or IL-18 mRNA expression. The data support the hypothesis that IP-10 is responsible for the recruitment of Th1 cells and monocytes in chronic hepatitis C, and suggest that its role in chronic hepatitis B is less determining. Moreover, they deliver additional support for the view that IFN-gamma still has to be considered as a mediator that determines the outcome of inflammation, e.g., via its ability to activate IL-18 expressing cells and to initiate a delayed type hypersensitivity reaction. (C) 2003 Wiley-Liss, Inc.
引用
收藏
页码:562 / 570
页数:9
相关论文
共 35 条
[1]   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
[2]   QUANTITATION OF HEPATITIS-C VIRUS-RNA IN LIVER-TRANSPLANT RECIPIENTS [J].
CHAZOUILLERES, O ;
KIM, M ;
COMBS, C ;
FERRELL, L ;
BACCHETTI, P ;
ROBERTS, J ;
ASCHER, NL ;
NEUWALD, P ;
WILBER, J ;
URDEA, M ;
QUAN, S ;
SANCHEZPESCADOR, R ;
WRIGHT, TL .
GASTROENTEROLOGY, 1994, 106 (04) :994-999
[3]   INVOLVEMENT OF THE DOUBLE-STRANDED-RNA-DEPENDENT KINASE PKR IN INTERFERON EXPRESSION AND INTERFERON-MEDIATED ANTIVIRAL ACTIVITY [J].
DER, SD ;
LAU, AS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (19) :8841-8845
[4]   Interleukin-18 [J].
Dinarello, CA .
METHODS-A COMPANION TO METHODS IN ENZYMOLOGY, 1999, 19 (01) :121-132
[5]   Semiquantitative analysis of intrahepatic cytokine mRNAs in chronic hepatitis C [J].
Dumoulin, FL ;
Bach, A ;
Leifeld, L ;
ElBakri, M ;
Fischer, HP ;
Sauerbruch, T ;
Spengler, U .
JOURNAL OF INFECTIOUS DISEASES, 1997, 175 (03) :681-685
[6]   SHORT-TERM PREDNISONE THERAPY AFFECTS AMINOTRANSFERASE ACTIVITY AND HEPATITIS-C VIRUS-RNA LEVELS IN CHRONIC HEPATITIS-C [J].
FONG, TL ;
VALINLUCK, B ;
GOVINDARAJAN, S ;
CHARBONEAU, F ;
ADKINS, RH ;
REDEKER, AG .
GASTROENTEROLOGY, 1994, 107 (01) :196-199
[7]   Human IP-10 selectively promotes dominance of polyclonally activated and environmental antigen-driven IFN-γ over IL-4 responses [J].
Gangur, V ;
Simons, FER ;
Hayglass, KT .
FASEB JOURNAL, 1998, 12 (09) :705-713
[8]   Caspase-1 processes IFN-gamma-inducing factor and regulates LPS-induced IFN-gamma production [J].
Ghayur, T ;
Banerjee, S ;
Hugunin, M ;
Butler, D ;
Herzog, L ;
Carter, A ;
Quintal, L ;
Sekut, L ;
Talanian, R ;
Paskind, M ;
Wong, W ;
Kamen, R ;
Tracey, D ;
Allen, H .
NATURE, 1997, 386 (6625) :619-623
[9]   Activation of interferon-gamma inducing factor mediated by interleukin-1 beta converting enzyme [J].
Gu, Y ;
Kuida, K ;
Tsutsui, H ;
Ku, G ;
Hsiao, K ;
Fleming, MA ;
Hayashi, N ;
Higashino, K ;
Okamura, H ;
Nakanishi, K ;
Kurimoto, M ;
Tanimoto, T ;
Flavell, RA ;
Sato, V ;
Harding, MW ;
Livingston, DJ ;
Su, MSS .
SCIENCE, 1997, 275 (5297) :206-209
[10]   Blocking chemokine responsive to γ-2/interferon (IFN)-γ inducible protein and monokine induced by IFN-γ activity in vivo reduces the pathogenetic but not the antiviral potential of hepatitis B virus-specific cytotoxic T lymphocytes [J].
Kakimi, K ;
Lane, TE ;
Wieland, S ;
Asensio, VC ;
Campbell, IL ;
Chisari, FV ;
Guidotti, LG .
JOURNAL OF EXPERIMENTAL MEDICINE, 2001, 194 (12) :1755-1766