High inflammatory activity is associated with an increased amount of IFN-gamma transcripts in peripheral blood cells of patients with chronic hepatitis C virus infection.
The mechanisms underlying the chronic hepatic inflammatory process in hepatitis C virus (HCV) infection are not well understood. Some models of experimentally induced hepatitis point to a role of interferon-gamma (IFN-gamma) secreted by liver-infiltrating peripheral blood lymphocytes (PBMC) in mediating hepatocellular injury. In the present study, IFN-gamma gene expression was analysed in PBMC and in liver biopsy specimens from patients with chronic HCV infection using a quantitative reverse transcriptase polymerase chain reaction technique. IFN-gamma gene expression by PBMC from HCV-infected patients exhibiting elevated serum transaminase activities was found to be increased up to ninefold when compared with (1) healthy individuals, (2) HCV-infected patients exhibiting normal or only slightly elevated serum enzyme activities, or (3) patients with drug-induced elevated serum transaminase activity. A histo-pathological evaluation of liver biopsy sections revealed further that high IFN-gamma gene expression by PBMC was associated with a more pronounced degree of inflammatory activity. In individual patients, the expression of IFN-gamma by PBMC was shown to parallel closely serum transaminase activities during IFN-alpha 2a therapy. Moreover, liver biopsy material from patients chronically infected with HCV contained higher amounts of IFN-gamma transcripts than liver tissue from patients with liver disorders unrelated to HCV infection or without any liver disease. These data thus demonstrate a close association between the amount of IFN-gamma transcripts in PBMC and in liver tissue and the inflammatory activity in chronic HCV infection in man.
Mihm
S
S
Department of Internal Medicine, Georg-August-Universität, Göttingen, Germany.
Hutschenreiter
A
A
Fayyazi
A
A
Pingel
S
S
Ramadori
G
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use; D001706:Biopsy; D002908:Chronic Disease; D005260:Female; D006526:Hepatitis C / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D008099:Liver / Q000473:pathology*; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis*
D000998:Antiviral Agents; D016898:Interferon-alpha; D012333:RNA, Messenger; D007371:Interferon-gamma; D000410:Alanine Transaminase