Cytokine mRNA expression in hepatitis C virus infection: TH1 predominance in patients with chronic hepatitis C and TH1-TH2 cytokine profile in subjects with self-limited disease.
Many determinants of the immune response have been implied in the pathogenesis of chronic hepatitis C. TH1 and TH2 cytokines play a prominent role in viral infections and a dysregulation of these cytokines could account for viral persistence and evolution of chronic disease. To explore a possible TH1 and TH2 cytokine dysregulation resulting in the inability to terminate hepatitis C virus (HCV) infection, we studied TH1 [interferon (IFN)-gamma, interleukin (IL)-2] and TH2 (IL-4, IL-10) mRNA expression of peripheral blood mononuclear cells (PBMC) in response to NS3 HCV antigen stimulation, in 31 untreated patients with chronic hepatitis C and 29 subjects with self-limited disease. After a 48 h culture of PBMC, total RNA isolation was performed and complementary DNA was prepared by reverse transcription. mRNA levels were quantified by real-time polymerase chain reaction using a standard curve formed after cloning each cytokine gene and a reference gene using recombinant DNA technology in a specific plasmid vector. In the patients group, mRNA expression of IFN-gamma, IL-2 and IL-4 but not IL-10 was detected, IFN-gamma being the predominant cytokine expressed. All four cytokines were expressed in subjects with self limited disease, however levels of IFN-gamma were lower and a significant higher expression of IL-10 compared to patients was found. There was a significant correlation between IFN-gamma mRNA expression levels and stage of fibrosis. Our findings show that in chronic hepatitis C, TH1 cytokines predominate and correlate to liver immunopathology. Furthermore, subjects with self-limited disease, maintain the ability to respond to HCV antigens for a long time after disease resolution.
Gigi
E
E
Second Medical Department, Aristotle University Medical School, Thessaloniki, Greece. gileina@yahoo.gr
Raptopoulou-Gigi
M
M
Kalogeridis
A
A
Masiou
S
S
Orphanou
E
E
Vrettou
E
E
Lalla
T H
TH
Sinakos
E
E
Tsapas
V
V
D000293:Adolescent; D000328:Adult; D000368:Aged; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*
D016207:Cytokines; D012333:RNA, Messenger; D016753:Interleukin-10; D007371:Interferon-gamma