Ribavirin in cancer immunotherapies: controlling nitric oxide helps generate cytotoxic lymphocyte.
Either ribavirin, RBV, or cyclophosphamide, CY, can shift an immune response from Th2 towards a Th1 cytokine profile. CY is used in this role in various current cancer immunotherapy attempts but with mixed success. More potent and reliable immunoadjuvants and Th 1 response biasing methods are needed. RBV is used today mainly to augment interferon-alpha treatment of hepatitis C. RBV shifts an immune response from Th2 towards Th1 more effectively than CY and may be a safe and useful adjuvant for current cancer immunotherapeutic efforts. RBV is thought to act by inhibition of tetrahydrobiopterin synthesis. Tetrahydrobiopterin is an essential co-factor for all known isoforms of nitric oxide synthase. Lowered nitric oxide favors Th1 development as high levels favor Th2 weighting.
Kast
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College of Medicine, University of Vermont, 2 Church St., Burlington, Vermont 05401, USA. rekast@email.com
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006526:Hepatitis C / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007167:Immunotherapy; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D012254:Ribavirin / Q000627:therapeutic use*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D009569:Nitric Oxide; D012254:Ribavirin; D007371:Interferon-gamma; D003520:Cyclophosphamide; D019001:Nitric Oxide Synthase