Th1/Th2 cytokine profiles and their relationship to clinical features in patients with chronic hepatitis C virus infection.
OBJECTIVE
An imbalance in helper T-cell type 1 (Th1) and type 2 (Th2) cytokines is suggested to play an important role in the pathogenesis of chronic viral infections, but this issue is not resolved in patients with hepatitis C virus (HCV) infection. The aim of this study was to clarify the relationship between the balance of Th1 and Th2 cytokines and liver damage.


METHODS
We investigated cytokine levels in the peripheral blood and liver tissue of patients with chronic HCV infection (n = 59) by three different methods; we used flow cytometry to detect intracellular cytokines, and we measured cytokine titers in sera and in the supernatants of lymphocyte cultures with enzyme-linked immunosorbent assays (ELISAs).


RESULTS
In both CD4+ and CD8+ cells, interferon (IFN) gamma-producing cell populations increased, while there was no difference in interleukin (IL)-10 production, indicating a shift to a Th1 cytokine profile with the progression of liver disease. With respect to the ratio of IFN-gamma to IL-10, a correlation was found in CD4+ cells between peripheral blood and liver tissue (r = 0.98; P = 0.0011). Th1 cytokine was predominant in intrahepatic CD4+ cells, while it was predominant in peripheral blood CD8+ cells.


CONCLUSIONS
These findings indicate a correlation between dominant Th1 response and disease activity and progression. In addition, we suggest that intrahepatic CD4+ T cells play a pathogenetic role in the hepatic injury of HCV infection.
Sobue
S
S
First Department of Internal Medicine, Medical School, Nagoya City University, Nagoya, Japan.
Nomura
T
T
Ishikawa
T
T
Ito
S
S
Saso
K
K
Ohara
H
H
Joh
T
T
Itoh
M
M
Kakumu
S
S
D000368:Aged; D018791:CD4 Lymphocyte Count; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D016174:Hepacivirus / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D008222:Lymphokines / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D008222:Lymphokines; D016753:Interleukin-10; D007371:Interferon-gamma