Ribavirin in cancer immunotherapies: controlling nitric oxide helps generate cytotoxic lymphocyte

Cancer Biol Ther. Nov-Dec 2002;1(6):626-30. doi: 10.4161/cbt.310.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Antiviral Agents / therapeutic use*
  • Cyclophosphamide / therapeutic use
  • Enzyme Inhibitors / therapeutic use
  • Hepatitis C / drug therapy
  • Hepatitis C / immunology
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Immunotherapy*
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Ribavirin / therapeutic use*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Th1 Cells / immunology
  • Th2 Cells / immunology


  • Antiviral Agents
  • Enzyme Inhibitors
  • Immunosuppressive Agents
  • Nitric Oxide
  • Ribavirin
  • Interferon-gamma
  • Cyclophosphamide
  • Nitric Oxide Synthase