Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2003 Jan-Feb;5(1):3-8.
doi: 10.1016/s1476-5586(03)80011-8.

Ribavirin in cancer immunotherapies: controlling nitric oxide augments cytotoxic lymphocyte function

Richard E Kast  1
Affiliations
Review

Ribavirin in cancer immunotherapies: controlling nitric oxide augments cytotoxic lymphocyte function

Richard E Kast. Neoplasia. 2003 Jan-Feb.

Abstract

Either ribavirin (RBV) or cyclophosphamide (CY) can shift an immune response from Th2 toward 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 Th1 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 toward 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 cofactor for all known isoforms of nitric oxide synthase. Lowered nitric oxide favors Th1 development as high levels favor Th2 weighting.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Chemical structure of ribavirin: 244 Da, terminal half-life in humans, 298 hours.
Figure 2
Figure 2
Chemical structure of cyclophosphamide, 279 Da.
Figure 3
Figure 3
5,6,7,8-Tetrahydrobiopterin, BH4. The pteridine nucleus is numbered in standard fashion.
See this image and copyright information in PMC

References

    1. Fairbanks LD, Bofill M, Ruckemann K, Simmonds HA. Importance of ribonucleotide to proliferating T lymphocytes from healthy humans. J Biol Chem. 1995;270:29682–29689. - PubMed
    1. Brodsky RA. High dose cyclophosphamide for a plastic anemia and autoimmunity. Curr Opin Oncol. 2002;14:143–146. - PubMed
    1. Jankovic D, Liu Z, Gause WC. Th1 and Th2 cell commitment during infectious disease. Trends Immunol. 2001;22:450–473. - PubMed
    1. Martin S, Hibino T, Faust A, Kleemann R, Kolb H. Differential expression of ICAM-1 and LFA-1 versus L-selectin and VCAM-1 in insulitis of NOD mice and association with both Th-1 and Th2 infiltrates. J Autoimmun. 1996;9:637–643. - PubMed
    1. Rothe H, Faust A, Schade U, Kleemann R, Bosse G, Hibino T, Martin S, Kolb H. Cyclophosphamide treatment of female NOD mice causes enhanced iNOS and IFN-gamma, but not of Il-4. Diabetologia. 1994;37:1154–1158. - PubMed

LinkOut - more resources