Skip to main content
Log in

Cytokine and Nitric Oxide Production in the Acute Phase of Bacterial Cell Wall-Induced Arthritis

  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

We have investigated the temporal relationship among proinflammatory cytokine expression, nitric oxide (NO) production and joint inflammation in the acute phase of bacterial cell wall-derived peptidoglycan polysaccharide(PG/PS)-induced arthritis. Acute joint inflammation was induced in female LEW/N rats by a single intraperitoneal injection of PG/PS. Arthritis index and paw volume were quantified and joint histopathology was evaluated during acute joint inflammation (0–10 days). Tumor necrosis factor (TNF), interleukin-1 (IL-1) and interleukin-6 (IL-6) were determined by bioassay whereas nitric oxide (NO) was quantified by measuring serum nitrate/nitrite levels via the Griess procedure. We found that serum levels of TNF and serum IL-1 preceded the increase in IL-6 and NO production. Furthermore, the production of these proinflammatory cytokines and NO preceded bone erosion and osteoclast activity. Erosion of subchondral bone preceded pannus formation and cellular synovitis in the acute phase of PG/PS-induced arthritis. The temporal expression of TNF, IL-1, IL-6 and NO suggest a cascade of inflammatory mediators in which monocytes and macrophages respond to PG/PS with enhanced synthesis of TNF and IL-1, which may in turn promote the synthesis of IL-6 and NO. We postulate that one or more of these inflammatory events are responsible for initiating the subchondral bone erosion observed in acute joint inflammation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. CROMARTIE, W. J., J. C. CRADDOCK, J. H. SCHWAB, S. K. ANDERLE, and C. H. YANG. 1977. Arthritis in rats after systemic injection of streptococcal cells or cell walls. J. Exp. Med. 146:1585–1602.

    Google Scholar 

  2. CLARK, R. L., J. T. CUTTINO, JR., S. K. ANDERLE, W. J. CROMARTIE, and J. H. SCHWAB. 1979. Radiological analysis of arthritis in rats after systemic injection of streptococcal cell walls. Arthritis Rheum. 22: 25–35.

    Google Scholar 

  3. WILDER, R. L., J. B. ALLEN, L. M. WAHL, G. B. CALANDRA, and S. M. WAHL. 1983. The pathogenesis of group A streptococcal cell wall-induced polyarthritis in the rat: comparative studies in arthritis-resistant and-susceptible inbred rat strains. Arthritis Rheum. 26:1442–1451.

    Google Scholar 

  4. ALLEN, J. B. and R. L. WILDER. 1985. Regulation of susceptibility to bacterial cell wall-induced arthritis in rats. Arthritis Rheum. 28:1318–1319.

    Google Scholar 

  5. WILDER, R. L., J. B. ALLEN, and C. HANSEN. 1987. Thymus-dependent and-independent regulation of la antigen expression in situ by cells in the synovium of rats with streptococcal cell wall-induced arthritis: differences in site and intensity of expression in euthymic, athymic, and cyclosporin A-treated LEW and F344 rats. J. Clin. Invest. 79:1160–1171.

    Google Scholar 

  6. ALLEN, J. B., D. G. MALONE, S. M. WAHL, G. B. CALANDRA, and R. L. WILDER. 1985. Role of the thymus in streptococcal cell wall-induced arthritis and granuloma formation. Comparative studies of pathology and cell wall distribution in athymic and euthymic rats. J. Clin. Invest. 76:1042–1056.

    Google Scholar 

  7. DALLDORF, F. G., W. J. CROMARTIE, S. K. ANDERLE, R. L. CLARK, and J. H. SCHWAB. 1980. Relation of experimental arthritis to the distribution of streptococcal cell wall fragments. Am. J. Pathol. 100:383–391.

    Google Scholar 

  8. WILDER, R. L. 1988. Streptococcal cell wall-induced polyarthritis in rats. In: Handbook of Animal Models for the Rheumatic Diseases. Vol. 1. R. A. Greenwald and H. Diamond, Editors. Boca Raton, Florida. CRC Press., 33–44.

    Google Scholar 

  9. WAHL, S. M., J. B. ALLEN, K. OHURA, D. E. CHENOWETH, and A. R. HAND. 1991. IFN-γ inhibits inflammatory cell recruitment and the evolution of bacterial cell wall-induced arthritis. J. Immunol. 146:95–100.

    Google Scholar 

  10. ALLEN, J. B., C. L. MANTHEY, A. R. HAND, K. OHURA, L. ELLINGSWORTH, and S. M. WAHL. 1990. Rapid onset of synovial inflammation and hyperplasia induced by transforming growth factor b. J. Exp. Med. 171:231–247.

    Google Scholar 

  11. WAHL, S. M. 1994. Transforming growth factor b: The good, the bad and the ugly. J. Exp. Med. 180:1587–1590.

    Google Scholar 

  12. WAHL, S. M., J. B. ALLEN, K. L. HINES, T. IMAMICHI, A. M. WAHL, L. T. FURCHT, and J. B. MC CARTHY. 1994. Synthetic fibronectin peptides suppress arthritis in rats by interrupting leukocyte adhesion and recruitment. J. Clin. Invest. 94:655–662.

    Google Scholar 

  13. MC CARTNEY-FRANCIS, N., J. B. ALLEN, D. E. MIZEL, J. E. ALBINA, Q.-W. XIE, C. F. NATHAN, and S. M. WAHL. 1993. Suppression of arthritis by an inhibitor of nitric oxide synthase. J. Exp. Med. 178:749–754.

    Google Scholar 

  14. IGNARRO, L. J. 1989. Biological actions and properties of endothelium-derived nitric oxide formed and released from artery and vein. Cir. Res. 65:1–21.

    Google Scholar 

  15. STUEHR, D. J. and C. F. NATHAN. 1989. Nitric oxide: a macrophage product responsible for cytostasis and respiratory inhibition in tumor target cells. J. Exp. Med. 169:1543–1555.

    Google Scholar 

  16. LI, L., G. L. NICOLSON, and I. J. FIDLER. 1991. Direct in vitro lysis of metastatic tumor cells by cytokine-activated murine vascular endothelial cells. Cancer Res. 51:245–254.

    Google Scholar 

  17. GRISHAM, M. B., R. D. SPECIAN, and T. E. ZIMMERMAN. 1994. Effects of nitric oxide synthase inhibition on the pathophysiology observed in a model of chronic granulomatous colitis. J. Pharm. Exp. Therap. 271:1114–1124.

    Google Scholar 

  18. NUSSLER, A. K. and T. R. BILLIAR. 1993. Inflammation, immunoregulation, and inducible nitric oxide synthase. J. Leuk. Biol. 54:171–178.

    Google Scholar 

  19. DABBAGH, A. J., D. R. BLAKE, and C. J. MORRIS. 1992. Effect of iron complexes on adjuvant arthritis. Ann. Rheum. Dis. 51:516–521.

    Google Scholar 

  20. MISHELL, B. B. and S. M. SHIIGI, editors. 1980. Selected Methods in Cellular Immunology. W.H. Freeman and Co., New York. Pp22–23.

    Google Scholar 

  21. BRISTOL, L. A., S. K. DURUM, and S. P. EISENBURG. 1993. Differential regulation of group A streptococcal peptidoglycan-polysaccharide(PG/APS)-stimulated macrophage production of IL-1 by rat strains susceptible and resistant to PG/APS-induced arthritis. Cell. Immunol. 149:130–143.

    Google Scholar 

  22. RUFF, M. R. and G. E. GIFFORD. Tumor necrosis factor. In Lymphokines, Vol. 2. E. Pick, editor. Academic Press, New York. 235–273.

  23. NAKAI, S., K. MIZUMO, M. KANETA, and H. YOSHIKATSU. 1988. A simple, sensitive bioassay for the detection of interleukin-1 using human melanoma A375 cell line. Biochem. Biophys, Res. Comm. 154:1189–1196.

    Google Scholar 

  24. FREI, K., T. P. LEIST, A. MEAGER, P. GALLO, D. LEPPERT, R. M. ZINKERNAGEL, and A. FONTANA. 1988. Production of B cell stimulatory factor-2 and inferferon-g in the central nervous system during viral meningitis and encephalitis. Evaluation in a murine model infection and in patients. J. Exp. Med. 168:449–453.

    Google Scholar 

  25. MOSMANN, T. 1983. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Meth. 65:55–63.

    Google Scholar 

  26. GRISHAM, M. B., G. G. JOHNSON, M. D. GAUTREAUX, and R. D. BERG. 1995. Measurement of nitrate and nitrite in extracellular fluids: A window to systemic nitric oxide determination. Methods 7:84–90.

    Google Scholar 

  27. DUFF, G. W. 1994. Cytokines and acute phase proteins in rheumatoid arthritis. Scand. J. Rheumatol. 23(Suppl 100):9–19.

    Google Scholar 

  28. WAHL, S. M., D. A. HUNT, J. B. ALLEN, R. L. WILDER, L. PAGLIA, and A. R. HAND. 1986. Bacterial cell wall-induced hepatic granulomas. A in vivo model of T cell dependent fibrosis. J. Exp. Med. 163:884–902.

    Google Scholar 

  29. AREND, W. P. and J. M. DAYER. 1990. Cytokines and cytokine inhibitors or antagonists in rheumatoid arthritis. Arthritis Rheum. 33:305–315.

    Google Scholar 

  30. AKIRA, S., T. TAGA, and T. KISHIMOTO. 1993. Interleukin-6 in biology and medicine. Adv. Immunol. 54:1–78.

    Google Scholar 

  31. STREITER, R. M., S. L. KUNKEL, H. J. SHOWELL, D. G. REMICK, S. H. PHAN, P. A. WARD, and R. M. MARKS. 1989. Endothelial cell gene expression of a neutrophil chemotactic factor by TNFα, LPS and IL1/3. Science 243:1467–1469.

    Google Scholar 

  32. POBER, J. S., M. A. GIMBRONE, JR., L. A. LAPIERRE, D. L. MENDRICK, W. FRIES, R. ROTHLEIN, and T. A. SPRINGER. 1986. Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor and immune interferon. J. Immunol. 137:1893–1896.

    Google Scholar 

  33. BEVILACQUA, M. P., J. S. POBER, M. E. WHELLER, R. S. COTRAN, and M. A. GIMBRONE JR. 1985. Interleukin-1 acts on cultured human vascular endothelium to increase the adherence of polymorphonuclear leukocytes, monocytes and related leukocyte cell lines. J. Clin. Invest. 76:975–983.

    Google Scholar 

  34. BRENNAN, F. M., R. N. MAINI, and M. FELDMANN. 1992. TNFa A pivotal role in rheumatoid arthritis? Brit. J. Rheum. 31:293–298.

    Google Scholar 

  35. YOCUM, D. E., L. ESPARZA, S. DUBRY, J. B. BENJAMIN, R. VOLZ, and P. SCUDERI. 1989, Characteristics of tumor necrosis factor production in rheumatoid arthritis. Cell Immunol. 122:131–145.

    Google Scholar 

  36. HOPKINS, S. J. and A. MEAGER. 1988. Cytokines in synovial fluid. II. The presence of tumor necrosis factor and interferon. Clin. Exp. Immunol. 73:88–92.

    Google Scholar 

  37. HUSBY, G. and R. C. WILLIAMS, JR. 1988. Synovial localization of tumor necrosis factor in patients with rheumatoid arthritis. J. Autoimmun. 1:363–371.

    Google Scholar 

  38. CHU, C. Q., M. FIELD, M. FELDMANN, and R. N. MAINI. 1991. Localization of tumor necrosis factor α in synovial tissue and at the cartilage-pannus junction in patients with rheumatoid arthritis. Arthritis Rheum. 34:1125–1132.

    Google Scholar 

  39. DELEURAN, B. W., C.-Q. CHU, M. FIELD, F. M. BRENNAN, T. MITCHELL, M. FELDMANN, and R. N. MAINI. 1992. Localization of tumor necrosis factor receptors in the synovial tissue and cartilage-pannus junction in patients with rheumatoid arthritis. Implications for local actions of tumor necrosis factor a. Arthritis Rheum. 35:1170–1178.

    Google Scholar 

  40. BRENNAN, F. M., D. CHANTRY, A. JACKSON, R. MAINI, and M. FELDMANN. 1989. Inhibitory effect of TNF α antibodies on synovial cell interleukin-l production in rheumatoid arthritis. Lancet 11:244–247.

    Google Scholar 

  41. WILLIAMS, R. O., M. FELDMANN, and R. N. MAINI. 1992. Anti-tumor necrosis factor ameliorates joint disease in murine collagen-induced arthritis. Proc. Natl. Acad. Sci. U.S.A. 89:9784–9788.

    Google Scholar 

  42. PIQUET, P. F., G. E. GRAU, C. VESIN, H. LOETSCHER, R. GENTZ, and W. LESSLAUER. 1992. Evolution of collagen arthritis in mice is arrested by treatment with anti-tumor necrosis factor (TNF) antibody or a recombinant soluble TNF receptor. Immunology 77:510–514.

    Google Scholar 

  43. MAINI, R. N., F. M. BRENNAN, R. WILLIAMS, C. Q. CHU, A. P. COPE, D. GIBBONS, and M. ELLIOTT. 1993. TNF-α in rheumatoid arthritis and prospects of anti-TNF therapy. Clin. Exp. Rheum. 11(Suppl. 8)S173–S175.

    Google Scholar 

  44. M. J. ELLIOTT, R. N. MAINI, M. FELDMANN, A. LONG-FOX, P. CHARLES, P. KATSIKIS, F. M. BRENNAN, J. WALKER, H. BIJL, J. GHRAYEB, and J. N. WOODY. 1993. Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumor necrosis factor α. Arthritis and Rheum. 36:1681–1690.

    Google Scholar 

  45. SYMONS, J. A., N. C. WOOD, F. S.DI GIOVINE, and G. W. DUFF. 1988. Soluble IL-2 receptor in rheumatoid arthritis: correlation with disease activity, IL-1 and IL-1 inhibition. J. Immunol. 141:2612–2618.

    Google Scholar 

  46. EASTGATE, J. A., J. A. SYMONS, N. C. WOOD, S. J. CAPPER, and G. W. DUFF. 1991. Plasma levels of interleukin-l alpha in rheumatoid arthritis. Br. J. Rheumatol. 30:295–297.

    Google Scholar 

  47. MAURY, C. P., L. C. ANDERSON, A. M. TEPPO, S. PARTANEN, and E. JU-VONEN. 1988. Mechanism of anaemia in rheumatoid arthritis: demonstration of raised interleukin-l beta concentrations in anaemic patients and of interleukin-l mediated suppression of normal erythropoiesis and proliferation of human erythroleukaemia (HEL) cells in vitro. Ann. Rheum. Dis. 47:972–978.

    Google Scholar 

  48. MIYASAKA, N., K. SATO, M. GOTO, M. SASANO, M. NATSUYAMA, K. INOUE, N. SASANO, M. NATSUYAMA, and K. NISHIOKA. 1988. Augmented interleukin-1 production and HLA-DR expression in the synovium of rheumatoid arthritis patients: possible involvement in joint destruction. Arthritis Rheum. 31:480–486.

    Google Scholar 

  49. EASTGATE, J. A., J. A. SYMONS, N. C. WOOD, F. M. GRINLINTON, F. S.DI GIOVINE, and G. W. DUFF. 1988. Correlation of plasma interleukin-1 levels with disease activity in rheumatoid arthritis. Lancet 2:706–709.

    Google Scholar 

  50. SHORE, A., S. JAGLAL, and E. C. KEYSTONE. 1986. Enhanced interleukin 1 generation by monocytes in vitro is temporally linked to early events in the onset or exacerbation of rheumatoid arthritis. Clin. Exp. Immunol. 65:293–302.

    Google Scholar 

  51. VAN DEN BERG, W. B., L. A. B. JOOSTEN, M. HELSEN, and F. A. J.VAN DE LOO. 1994. Amelioration of established murine collagen-induced arthritis with anti-IL-1 treatment. Clin. Exp. Immunol. 95:237–243.

    Google Scholar 

  52. VAN DE Loo, A. A. J., O. J. ARNTZ, A. C. BAKKER, P. L. E. M.VAN LENT, M. J. M. JACOBS, and W. B.VAN DEN BERG. 1995. Role of interleukin 1 in antigen-induced exacerbations of murine arthritis. Am. J. Path. 146:239–249.

    Google Scholar 

  53. MAKAROV, S. S., J. C. OLSEN, W. N. JOHNSON, S. K. ANDERLE, R. R. BROWN, A. S. BALDWIN, J. S. HASKILL, and J. H. SCHWAB. 1996. Suppression of experimental arthritis by gene transfer of interleukin 1 receptor antagonist cDNA. Proc. Natl. Acad. Sci. U.S.A. 93:402–406.

    Google Scholar 

  54. ISSEKUTZ, A. C., A. MEAGER, I. OTTERNESS, and T. B. ISSEKUTZ. 1994. The role of tumor necrosis factor-alpha and IL-1 in polymorphonuclear leukocyte and T lymphocyte recruitment to joint inflammation in adjuvant arthritis. Clin. Exp. Immunol. 97:26–32.

    Google Scholar 

  55. VAN DE Loo, F. A. J., L. A. B. JOOSTEN, P. L. E. M.VAN LENT, O. J. ARNTZ, and W. B.VAN DEN BERG. 1995. Role of interleukin-1 tumor necrosis factor α and interleukin-6 in cartilage proteoglycan metabolism and destruction. Effect of in situ blocking in murine antigen-and zymosan-induced arthritis. Arthritis Rheum. 38:164–172.

    Google Scholar 

  56. PETTIPHER, E. R., G. A. HIGGS, and B. HENDERSON. 1986. Interleukin-1 induces leukocyte infiltration and cartilage proteoglycan degradation in the synovial joint. Proc. Natl. Acad. Sci. U.S.A. 83:8749–8753.

    Google Scholar 

  57. MANOLIOS, N., C. GECZY, and L. SCHRIEBER. 1991. Lymphocyte migration in health and inflammatory rheumatic disease. Semin. Arthritis Rheum. 20:339–352.

    Google Scholar 

  58. POBER, J. S. and R. S. COTRAN. 1990. Cytokines and endothelial cell biology. Physiol. Rev. 70:27–52.

    Google Scholar 

  59. OPPENHEIM, J. J., C. O. C. ZACHARIAE, N. MUKADIA, and K. MATSUSHIMA. 1991. Properties of the novel proinflammatory supergene “intercine” cytokine family. Ann. Rev. Immunol. 9:617–648.

    Google Scholar 

  60. KOCH, A. E., S. L. KUNKEL, L. A. HARLOW, B. JOHNSON, H. L. EVANOFF, G. K. HAINES, M. D. BURDICK, R. M. POPE, and R. M. STRIETER. 1992. Enhanced production of monocyte chemoattractant protein-1 in rheumatoid arthritis. J. Clin. Invest. 90:722–729.

    Google Scholar 

  61. WILDER, R., P. J. CASE, L. J. CROFFORD, G. K. KUMKUMIAN, R. LAFYATIS, E. F. REMMERS, H. SANO, E. M. STERNBERG, and D. E. YOCUM. 1991. Endothelial cells and the pathogenesis of rheumatoid arthritis in humans and streptococcal cell wall arthritis in Lewis rats. J. Cell Biochem. 45:162–166.

    Google Scholar 

  62. HAYASHIDA, K., T. OCHI, M. FUJIMOTO, H. OWAKI, Y. SHIMAOKA, K. ONO, and K. MATSUMOTO. 1992. Bone-marrow changes in adjuvant-induced and collagen-induced arthritis. Interleukin-1 and interleukin-6 activity and abnormal myelopoiesis. Arthritis Rheum. 35:241–245.

    Google Scholar 

  63. HOUSSIAU, F. A., J. P. DEVOGELAER, J. VAN DAMME, C. N. DE DEUXCHAISNES, and J. VAN SNICK, 1988. Inteleukin-6 in synovial fluid and serum of patients with rheumatoid arthritis and other inflammatory arthritides. Arthritis Rheum. 31:784–788.

    Google Scholar 

  64. HIRANO, T., T. MATSUDA, M. TURNER, N. MIYASAKA, G. BUCHAN, B. TANG, K. SATO, M. SHIMIZU, R. MAINI, M. FELDMANN, and T. KISHIMOTO. 1988. Excessive production of interleukin 6/B cell stimulatory factor-2 in rheumatoid arthritis. Eur. J. Immunol. 18:1791–1801.

    Google Scholar 

  65. MIYASAKA, N., K. SATO, M. GOTO, M. SASANO, M. NATSUYAMA, K. INOUE, and K. NISHIOKA. 1988. Augmented interleukin-1 production and HLA-DR expression in the synovium of rheumatoid arthritis patients: a possible involvement in joint destruction. Arthritis Rheum. 31:480–486.

    Google Scholar 

  66. MIYASAKA, N., K. SATO, J. HASHIMOTO, H. KOHSAKA, K. YAMAMOTO, M. GOTO, K. INOUE, T. MATSUDA, T. HIRANO, T. KISHIMOTO, and K. NISHIOKA. 1989. Constitutive production of interleukin 6/B cell stimulatory factor-2 from inflammatory synovium. Clin. Immunol. Immunopathol. 52:238–247.

    Google Scholar 

  67. JILKA, R. L., G. HANGOC, G. GIRASOLE, G. PASSERI, D. C. WILLIAMS, J. S. ABRAMS, B. BOYCE, H. BROXMEYER, and S. C. MANOLAGAS. 1992. Increased osteoclasts development after estrogen loss: Mediation by interleukin-6. Science 257:88–91.

    Google Scholar 

  68. GUERNE, P. A., B. L. ZURAW, J. H. VAUGHAN, D. A. CARSON, and M. LOTZ. 1989. Synovium as a source of interleukin-6 in vitro. J. Clin. Invest. 83:585–592.

    Google Scholar 

  69. ISHIMI, Y., C. MIYAURA, C. H. JIN, T. AKATSU, E. ABE, Y. NAKAMURA, A. YAMAGUCHI, S. YOSHIKI, T. MATSUDA, T. HIRANO, T. KISHIMOTO, and T. SUDA. 1990. IL-6 is produced by osteoblasts and induces bone resorption. J. Immunol. 145:3297–3303.

    Google Scholar 

  70. FIRESTEIN, G. S. and N. J. ZVAIFLER. 1990. How important are T cells in chronic rheumatoid arthritis. Arthritis Rheum. 33:768–772.

    Google Scholar 

  71. FIRESTEIN, G. S. 1994. Rheumatoid arthritis and pannus. In: Klippel J.H., Dieppe P., eds. Rheumatology, London, Gower Publications, Mosby-Year Book, Europe Ltd. 3(12):1–30.

    Google Scholar 

  72. DE LA MATA, J., H. L. UY, T. A. GUISE, B. STORY, B. F. BOYCE, G. R. MUNDY, and G. D. ROODMAN. 1995. Interleukin-6 enhances hypercalcemia and bone resorption mediated by parathyroid hormone-related protein in vivo. J. Clin. Invest. 95:2846–2852.

    Google Scholar 

  73. LOWIK, C. W. G. M., G.VAN DER PLUIJIM, H. BLYOYS, K. HOEKMAN, O. L. M. BIJVOET, L. A. AARDEN, and S. E. PAPAPOULOS. 1989. Parathyroid hormone(PTH) and PTH-like protein(PLP) stimulate interleukin-6 production by osteogenic cells: A possible role of interleukin-6 in osteoclastogenesis. Biochem. Biophys. Res. Commun. 162:1546–1552.

    Google Scholar 

  74. FEYEN, J. H. M., P. ELFORD, F. E. DI PADOVA, and U. TRESHSEL. 1989. Interleukin-6 is produced by bone and modulated by parathyroid hormone. J. Bone Miner. Res. 4:633–638.

    Google Scholar 

  75. KURIHARA, H., D. BERTOLINI, T. SUDA, Y. AKIYAM, and G. D. ROODMAN. 1990. IL-6 stimulates osteoclasts-like multinucleated cell formation in long term human marrow cultures by inducing IL-1 release. J. Immunol. 144:4226–4230.

    Google Scholar 

  76. BLACK, K., I. R. GARRETT, and G. R. MUNDY. 1991. Chinese hamster cells transfected with the murine interleukin-6 gene cause hypercalcemia as well as cachexia, leukocytosis and thrombocytosis in tumor-bearing nude mice. Endocrinology 128:2657–2659.

    Google Scholar 

  77. RALSTON, S. H., D. TODD, M. HELFRICH, N. BENJAMIN, and P. S. GRABOWSKI. 1994. Human osteoblasts-like cells produce nitric oxide and express inducible nitric oxide synthase. Endocrinology 135:330–336.

    Google Scholar 

  78. MARCINKIEWICZ, J., A. GRABOWSKA, and B. CHAIN. 1995. Nitric oxide up-regulates the release of inflammatory mediators by mouse macrophages. Eur. J. Immunol. 25:947–951.

    Google Scholar 

  79. ZVAIFLER N. J. 1995. Macrophages and the synovial lining. Scand. J. Rheum. 24:67–75.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fuseler, J.W., Conner, E.M., Davis, J.M. et al. Cytokine and Nitric Oxide Production in the Acute Phase of Bacterial Cell Wall-Induced Arthritis. Inflammation 21, 113–131 (1997). https://doi.org/10.1023/A:1027351111240

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1027351111240

Keywords

Navigation