Treatment with ribavirin and interferon-alpha reduces interferon-gamma expression in patients with chronic hepatitis C.
Recent studies in vitro and in animals have suggested that ribavirin may potentiate the antihepatitis C virus (HCV) activity of interferon-alpha (IFN-alpha) by up-modulating the production of T cell-derived cytokines, such as interleukin (IL)-2 and IFN-gamma, which play a key role in the cellular immune response against HCV. To study the immune-modulatory mechanisms of ribavirin further, cytokine production by activated T cells and circulating cytokine levels were studied by FACS analysis and ELISA testing in 25 patients with chronic hepatitis C unresponsive to IFN-alpha, before and after treatment with either ribavirin plus IFN-alpha or IFN-alpha alone. After 16 weeks of treatment, both the expression of IFN-gamma by activated T cells and the blood levels of IFN-gamma, were significantly reduced with respect to pretreatment values in patients treated with ribavirin and IFN-alpha but not in those undergoing treatment with IFN-alpha alone. The expression of IFN-gamma was significantly lower in patients that gained normal ALT levels with respect to those that did not. No modification of the expression of IL-2, IL-4 and IL-10 was found before and after treatment in either group of patients. In conclusion, the results of this study do not support up-modulation of IFN-gamma and IL-2 production as the mechanism by which ribavirin potentiates IFN-alpha anti HCV activity. In addition, our findings suggest that ribavirin may exert an anti-inflammatory effect and may help reducing IFN-gamma-driven T cell activation and liver damage.
Bergamini
A
A
Department of Public Health, University of Rome Tor Vergata Rome, Italy. bergamini@med.uniroma2.it
Bolacchi
F
F
Cepparulo
M
M
Demin
F
F
Uccella
I
I
Bongiovanni
B
B
Ombres
D
D
Angelico
F
F
Liuti
A
A
Hurtova
M
M
Francioso
S
S
Carvelli
C
C
Cerasari
G
G
Angelico
M
M
Rocchi
G
G
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D012254:Ribavirin / Q000494:pharmacology*; D019562:Viral Load
D000276:Adjuvants, Immunologic; D016898:Interferon-alpha; D007376:Interleukin-2; D016753:Interleukin-10; D015847:Interleukin-4; D012254:Ribavirin; D007371:Interferon-gamma