Lack of evidence for the Th2 predominance in patients with chronic hepatitis C.
A T helper (Th)1 to Th2 shift has been proposed to be a critical pathogenic determinant in chronic hepatitis C. Here, we evaluated mitogen-induced and hepatitis C virus (HCV) core antigen-induced cytokine production in 28 patients with biopsy-proven chronic hepatitis C. Flow cytometry demonstrated that after mitogenic stimulation the percentage of Th2 cells (IL-4 + or IL-13 +) and Th0 cells (IFN-gamma/IL-4 + or IL-2/IL-13 +) did not differ between patients and controls. In contrast, the percentage of Th1 cells (IFN-gamma + or IL-2 +) was significantly increased in CD4 +, CD8 +, 'naive'-CD45RA + and 'memory'-CD45RO + T-cell subsets from patients versus controls. Similar results were obtained by ELISA testing supernatants from mitogen-stimulated, unfractionated peripheral blood mononuclear cell (PBMC) cultures. Interferon-alpha treatment was associated with a reduction in the mitogen-induced Th1 cytokine response in those patients who cleared their plasma HCV-RNA. Analysis of cytokine expression by CD4 + T cells after HCV core antigen stimulation in a subgroup of 13 chronic hepatitis C patients demonstrated no cytokine response in 74% of these patients and an IFN-gamma-restricted response in 26%. Finally, no Th2 shift was found in lipopolysaccharide-stimulated monocytes. These data indicate that a Th1 to Th2 shift does not occur in chronic hepatitis C.
Bergamini
A
A
Department of Public Health and Cellular Biology, University of Rome Tor Vergata, Rome, Italy. bergamini@med.uniroma2.it
Bolacchi
F
F
Cerasari
G
G
Carvelli
C
C
Faggioli
E
E
Cepparulo
M
M
Demin
F
F
Uccella
I
I
Bongiovanni
B
B
Niutta
P
P
Capozzi
M
M
Lupi
M
M
Piscitelli
E
E
Rocchi
G
G
Angelico
M
M
D000328:Adult; D000368:Aged; D017252:CD3 Complex; D002458:Cell Fractionation; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007371:Interferon-gamma / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018448:Models, Immunological; D009000:Monocytes / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018418:Th2 Cells; D014758:Viral Core Proteins / Q000276:immunology
D017252:CD3 Complex; D016207:Cytokines; D016898:Interferon-alpha; D007378:Interleukins; D008070:Lipopolysaccharides; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D007371:Interferon-gamma