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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1993 Oct;110(2):701–706. doi: 10.1111/j.1476-5381.1993.tb13868.x

Modulation of adjuvant arthritis by endogenous nitric oxide.

A Ialenti 1, S Moncada 1, M Di Rosa 1
PMCID: PMC2175935  PMID: 8242242

Abstract

1. The role of endogenous nitric oxide (NO) in adjuvant arthritis in Lewis rats has been studied by use of L-arginine, the amino acid from which NO is synthesized, and NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase. Prolonged modulation (35 days) of the L-arginine: NO pathway in rats was achieved by dissolving test compounds in the drinking water (L-arginine: 3, 10 and 30 mg ml-1; L-NAME: 0.1, 1 and 10 mg ml-1). 2. Arthritis was exacerbated by L-arginine and suppressed by L-NAME in a dose-related fashion. Combined treatment with L-NAME (1 mg ml-1) and L-arginine (30 mg ml-1) did not modify the arthritis. 3. Reduced weight gain, which is a feature of adjuvant arthritis, was modified by these compounds so that L-arginine reduced weight gain whereas L-NAME increased weight gain compared with that in control animals. 4. D-Arginine (30 mg ml-1), NG-nitro-D-arginine methyl ester (D-NAME: 1 mg ml-1) and L-lysine (30 mg ml-1), an amino acid not involved in the generation of NO, were without effect on either arthritis or body weight gain. 5. Antigen-stimulated proliferation of T-lymphocytes as well as generation of nitrite (NO2-) and release of acid phosphatase from macrophages were all enhanced in L-arginine-treated arthritic rats and reduced in L-NAME-treated animals. 6. These results suggest that endogenous NO modulates adjuvant arthritis, possibly by interfering with the activation of T-lymphocytes and/or macrophages.

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Selected References

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  1. Albina J. E., Abate J. A., Henry W. L., Jr Nitric oxide production is required for murine resident peritoneal macrophages to suppress mitogen-stimulated T cell proliferation. Role of IFN-gamma in the induction of the nitric oxide-synthesizing pathway. J Immunol. 1991 Jul 1;147(1):144–148. [PubMed] [Google Scholar]
  2. Barbul A. Arginine: biochemistry, physiology, and therapeutic implications. JPEN J Parenter Enteral Nutr. 1986 Mar-Apr;10(2):227–238. doi: 10.1177/0148607186010002227. [DOI] [PubMed] [Google Scholar]
  3. Barbul A., Fishel R. S., Shimazu S., Wasserkrug H. L., Yoshimura N. N., Tao R. C., Efron G. Intravenous hyperalimentation with high arginine levels improves wound healing and immune function. J Surg Res. 1985 Apr;38(4):328–334. doi: 10.1016/0022-4804(85)90045-9. [DOI] [PubMed] [Google Scholar]
  4. Barbul A., Wasserkrug H. L., Seifter E., Rettura G., Levenson S. M., Efron G. Immunostimulatory effects of arginine in normal and injured rats. J Surg Res. 1980 Sep;29(3):228–235. doi: 10.1016/0022-4804(80)90165-1. [DOI] [PubMed] [Google Scholar]
  5. Beutler B., Cerami A. The biology of cachectin/TNF--a primary mediator of the host response. Annu Rev Immunol. 1989;7:625–655. doi: 10.1146/annurev.iy.07.040189.003205. [DOI] [PubMed] [Google Scholar]
  6. CABAUD P. G., WROBLEWSKI F. Colorimetric measurement of lactic dehydrogenase activity of body fluids. Am J Clin Pathol. 1958 Sep;30(3):234–236. doi: 10.1093/ajcp/30.3.234. [DOI] [PubMed] [Google Scholar]
  7. Cohen I. R. Autoimmunity to chaperonins in the pathogenesis of arthritis and diabetes. Annu Rev Immunol. 1991;9:567–589. doi: 10.1146/annurev.iy.09.040191.003031. [DOI] [PubMed] [Google Scholar]
  8. Cooper S. M., Sriram S., Ranges G. E. Suppression of murine collagen-induced arthritis with monoclonal anti-Ia antibodies and augmentation with IFN-gamma. J Immunol. 1988 Sep 15;141(6):1958–1962. [PubMed] [Google Scholar]
  9. Di Rosa M., Radomski M., Carnuccio R., Moncada S. Glucocorticoids inhibit the induction of nitric oxide synthase in macrophages. Biochem Biophys Res Commun. 1990 Nov 15;172(3):1246–1252. doi: 10.1016/0006-291x(90)91583-e. [DOI] [PubMed] [Google Scholar]
  10. GIANETTO R., DE DUVE C. Tissue fractionation studies. 4. Comparative study of the binding of acid phosphatase, beta-glucuronidase and cathepsin by rat-liver particles. Biochem J. 1955 Mar;59(3):433–438. doi: 10.1042/bj0590433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gardiner S. M., Compton A. M., Bennett T., Palmer R. M., Moncada S. Regional haemodynamic changes during oral ingestion of NG-monomethyl-L-arginine or NG-nitro-L-arginine methyl ester in conscious Brattleboro rats. Br J Pharmacol. 1990 Sep;101(1):10–12. doi: 10.1111/j.1476-5381.1990.tb12079.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Holoshitz J., Matitiau A., Cohen I. R. Arthritis induced in rats by cloned T lymphocytes responsive to mycobacteria but not to collagen type II. J Clin Invest. 1984 Jan;73(1):211–215. doi: 10.1172/JCI111193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Holoshitz J., Naparstek Y., Ben-Nun A., Cohen I. R. Lines of T lymphocytes induce or vaccinate against autoimmune arthritis. Science. 1983 Jan 7;219(4580):56–58. doi: 10.1126/science.6336851. [DOI] [PubMed] [Google Scholar]
  15. Hom J. T., Bendele A. M., Carlson D. G. In vivo administration with IL-1 accelerates the development of collagen-induced arthritis in mice. J Immunol. 1988 Aug 1;141(3):834–841. [PubMed] [Google Scholar]
  16. Ialenti A., Ianaro A., Moncada S., Di Rosa M. Modulation of acute inflammation by endogenous nitric oxide. Eur J Pharmacol. 1992 Feb 11;211(2):177–182. doi: 10.1016/0014-2999(92)90526-a. [DOI] [PubMed] [Google Scholar]
  17. Kirk S. J., Regan M. C., Barbul A. Cloned murine T lymphocytes synthesize a molecule with the biological characteristics of nitric oxide. Biochem Biophys Res Commun. 1990 Dec 14;173(2):660–665. doi: 10.1016/s0006-291x(05)80086-5. [DOI] [PubMed] [Google Scholar]
  18. Kröncke K. D., Kolb-Bachofen V., Berschick B., Burkart V., Kolb H. Activated macrophages kill pancreatic syngeneic islet cells via arginine-dependent nitric oxide generation. Biochem Biophys Res Commun. 1991 Mar 29;175(3):752–758. doi: 10.1016/0006-291x(91)91630-u. [DOI] [PubMed] [Google Scholar]
  19. Liew F. Y., Li Y., Moss D., Parkinson C., Rogers M. V., Moncada S. Resistance to Leishmania major infection correlates with the induction of nitric oxide synthase in murine macrophages. Eur J Immunol. 1991 Dec;21(12):3009–3014. doi: 10.1002/eji.1830211216. [DOI] [PubMed] [Google Scholar]
  20. McCall T. B., Feelisch M., Palmer R. M., Moncada S. Identification of N-iminoethyl-L-ornithine as an irreversible inhibitor of nitric oxide synthase in phagocytic cells. Br J Pharmacol. 1991 Jan;102(1):234–238. doi: 10.1111/j.1476-5381.1991.tb12159.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Moncada S., Palmer R. M., Higgs E. A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed] [Google Scholar]
  22. Park K. G., Hayes P. D., Garlick P. J., Sewell H., Eremin O. Stimulation of lymphocyte natural cytotoxicity by L-arginine. Lancet. 1991 Mar 16;337(8742):645–646. doi: 10.1016/0140-6736(91)92456-c. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Reynolds J. V., Daly J. M., Zhang S., Evantash E., Shou J., Sigal R., Ziegler M. M. Immunomodulatory mechanisms of arginine. Surgery. 1988 Aug;104(2):142–151. [PubMed] [Google Scholar]
  25. Thorbecke G. J., Shah R., Leu C. H., Kuruvilla A. P., Hardison A. M., Palladino M. A. Involvement of endogenous tumor necrosis factor alpha and transforming growth factor beta during induction of collagen type II arthritis in mice. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7375–7379. doi: 10.1073/pnas.89.16.7375. [DOI] [PMC free article] [PubMed] [Google Scholar]

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