Ribavirin increases mitogen- and antigen-induced expression of CD40L on CD4+ T cells in vivo.
Here, CD40L expression and cytokine production have been analysed in peripheral blood cells from orthotopic liver transplantation (OLT) recipients treated with ribavirin for recurrent chronic hepatitis C. The study included 18 OLT recipients treated with ribavirin, eight control OLT recipients and 10 healthy controls. FACS analysis showed that baseline expression of CD40L was not different between ribavirin-treated patients and controls. In contrast, after stimulation with both HCV core antigen and phorbol myristate acetate (PMA) plus ionomycin (IO), the expression of CD40L on CD4 lymphocytes was significantly higher in the ribavirin group compared with controls. In the ribavirin group, the increased expression of CD40L significantly correlated with reduction of HCV RNA levels with respect to pretreatment values. Finally, ribavirin treatment was not associated with modification of PMA-IO-induced cytokine production by T lymphocytes and interleukin (IL)-1beta and tumour necrosis-alpha (TNF)-alpha production by CD40L-stimulated monocytes. In conclusion, these data indicate that ribavirin -upmodulates CD40L expression on CD4 T cells, a property which may account in part for its ability to enhance the antiviral activity of interferon-alpha in the treatment of chronic HCV infection.
Bergamini
A
A
Department of Public Health and Cellular Biology, Chair of Infectious Diseases, University of Rome Tor Vergata, Rome, Italy. bergamini@med.uniroma2.it
Cepparulo
M
M
Bolacchi
F
F
Araco
A
A
Tisone
G
G
Ombres
D
D
Rocchi
G
G
Angelico
M
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology* / Q000627:therapeutic use; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D023201:CD40 Ligand / Q000096:biosynthesis*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D018936:Hepatitis C Antigens / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D008103:Liver Cirrhosis / Q000601:surgery; D016031:Liver Transplantation; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology; D009000:Monocytes / Q000276:immunology; D012367:RNA, Viral / Q000097:blood; D012008:Recurrence; D012254:Ribavirin / Q000494:pharmacology* / Q000627:therapeutic use; D014758:Viral Core Proteins / Q000276:immunology
D000276:Adjuvants, Immunologic; D000998:Antiviral Agents; D016207:Cytokines; D018936:Hepatitis C Antigens; D008934:Mitogens; D012367:RNA, Viral; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D023201:CD40 Ligand; D012254:Ribavirin