Abstract
Nitric oxide (NO) has recently been identified as a potent and pleiotropic intracellular mediator produced by and acting on many cells of the body. Although considerable attention has been devoted to the regulation of NO by inflammatory cytokines, and also to the role of NO as an important effector molecule in immune function, there is very little information on the role of this mediator in modulating T-cell-dependent cytokine production. In this study we show that physiological levels of NO (either produced by activated macrophages or by the addition of exogenous NO donors) can selectively down-regulate interleukin-3 (IL-3) production by spleen cells from contact-sensitized mice, while leaving IL-2 activity unaffected. Thus NO may have an important role as an immunomodulatory as well as effector molecule in the immune system.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Betz M., Fox B. S. Prostaglandin E2 inhibits production of Th1 lymphokines but not of Th2 lymphokines. J Immunol. 1991 Jan 1;146(1):108–113. [PubMed] [Google Scholar]
- Collier J., Vallance P. Second messenger role for NO widens to nervous and immune systems. Trends Pharmacol Sci. 1989 Nov;10(11):427–431. doi: 10.1016/s0165-6147(89)80001-x. [DOI] [PubMed] [Google Scholar]
- Hibbs J. B., Jr, Taintor R. R., Vavrin Z., Rachlin E. M. Nitric oxide: a cytotoxic activated macrophage effector molecule. Biochem Biophys Res Commun. 1988 Nov 30;157(1):87–94. doi: 10.1016/s0006-291x(88)80015-9. [DOI] [PubMed] [Google Scholar]
- Hoffman R. A., Langrehr J. M., Billiar T. R., Curran R. D., Simmons R. L. Alloantigen-induced activation of rat splenocytes is regulated by the oxidative metabolism of L-arginine. J Immunol. 1990 Oct 1;145(7):2220–2226. [PubMed] [Google Scholar]
- Kolb H., Kolb-Bachofen V. Nitric oxide: a pathogenetic factor in autoimmunity. Immunol Today. 1992 May;13(5):157–160. doi: 10.1016/0167-5699(92)90118-Q. [DOI] [PubMed] [Google Scholar]
- Liew F. Y., Li Y., Severn A., Millott S., Schmidt J., Salter M., Moncada S. A possible novel pathway of regulation by murine T helper type-2 (Th2) cells of a Th1 cell activity via the modulation of the induction of nitric oxide synthase on macrophages. Eur J Immunol. 1991 Oct;21(10):2489–2494. doi: 10.1002/eji.1830211027. [DOI] [PubMed] [Google Scholar]
- Liew F. Y., Millott S., Li Y., Lelchuk R., Chan W. L., Ziltener H. Macrophage activation by interferon-gamma from host-protective T cells is inhibited by interleukin (IL)3 and IL4 produced by disease-promoting T cells in leishmaniasis. Eur J Immunol. 1989 Jul;19(7):1227–1232. doi: 10.1002/eji.1830190712. [DOI] [PubMed] [Google Scholar]
- Marcinkiewicz J., Chain B. Antigen-specific inhibition of IL-2 and IL-3 production in contact sensitivity to TNP. Immunology. 1989 Oct;68(2):185–189. [PMC free article] [PubMed] [Google Scholar]
- Marcinkiewicz J. In vitro cytokine release by activated murine peritoneal macrophages: role of prostaglandins in the differential regulation of tumor necrosis factor alpha, interleukin 1, and interleukin 6. Cytokine. 1991 Jul;3(4):327–332. doi: 10.1016/1043-4666(91)90501-4. [DOI] [PubMed] [Google Scholar]
- Marcinkiewicz J., Radziszewski W., Chain B. M. Prostaglandin E2 (PGE2) differentially regulates the production of IL-2 and IL-3 by murine immune T-cells. Folia Histochem Cytobiol. 1992;30(1):1–4. [PubMed] [Google Scholar]
- Marletta M. A., Yoon P. S., Iyengar R., Leaf C. D., Wishnok J. S. Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate. Biochemistry. 1988 Nov 29;27(24):8706–8711. doi: 10.1021/bi00424a003. [DOI] [PubMed] [Google Scholar]
- Mills C. D. Molecular basis of "suppressor" macrophages. Arginine metabolism via the nitric oxide synthetase pathway. J Immunol. 1991 Apr 15;146(8):2719–2723. [PubMed] [Google Scholar]
- Moncada S., Palmer R. M., Higgs E. A. Biosynthesis of nitric oxide from L-arginine. A pathway for the regulation of cell function and communication. Biochem Pharmacol. 1989 Jun 1;38(11):1709–1715. doi: 10.1016/0006-2952(89)90403-6. [DOI] [PubMed] [Google Scholar]
- Palmer R. M., Ferrige A. G., Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11;327(6122):524–526. doi: 10.1038/327524a0. [DOI] [PubMed] [Google Scholar]
- Radomski M. W., Rees D. D., Dutra A., Moncada S. S-nitroso-glutathione inhibits platelet activation in vitro and in vivo. Br J Pharmacol. 1992 Nov;107(3):745–749. doi: 10.1111/j.1476-5381.1992.tb14517.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rees D. D., Palmer R. M., Schulz R., Hodson H. F., Moncada S. Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo. Br J Pharmacol. 1990 Nov;101(3):746–752. doi: 10.1111/j.1476-5381.1990.tb14151.x. [DOI] [PMC free article] [PubMed] [Google Scholar]