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. 1991 Feb;87(2):463–469. doi: 10.1172/JCI115018

Enhanced production of neutrophil-activating peptide-1/interleukin-8 in rheumatoid arthritis.

M Seitz 1, B Dewald 1, N Gerber 1, M Baggiolini 1
PMCID: PMC295098  PMID: 1899427

Abstract

Production of the neutrophil-activating peptide (NAP)-1/IL-8 by mononuclear phagocytes from patients with RA and from control subjects was studied under various conditions. Mononuclear cells from bone marrow (BMMC), PBMC, and synovial fluid (SFMC) were cultured for up to 48 h in the absence or presence of Escherichia coli LPS, different interleukins, interferon-gamma, zymosan, or immune complexes, and the neutrophil-stimulating activity released into the culture medium was determined. As shown by neutralization with an antiserum raised against human recombinant NAP-1/IL-8, over 90% of this activity could be attributed to NAP-1/IL-8. In unstimulated mononuclear cells from control individuals and BMMC from RA patients, the production of NAP-1/IL-8 was very low and was enhanced moderately by stimulation with LPS. By contrast, the spontaneous production of NAP-1/IL-8 was 3- to 10-fold higher in PBMC and even much higher in SFMC from RA patients. In all instances, the yield of NAP-1/IL-8 could be enhanced by stimulation in culture. In addition to LPS, rheumatoid factor-containing immune complexes, zymosan, and IL-1 were highly effective in inducing NAP-1/IL-8 production, while IL-3, GM-CSF, tumor necrosis factor (TNF), and IL-2 were somewhat less potent. An inhibitory effect was obtained with IFN-gamma, which significantly decreased the spontaneous NAP-1/IL-8 release from SFMC and the IL-1- and LPS-induced NAP-1/IL-8 from RA and control PBMC. Inhibition was also observed with glucocorticoids. The production of NAP-1/IL-8 was markedly reduced by dexamethasone in phagocytosis-stimulated PBMC, and almost totally inhibited in SFMC obtained from joints after intraarticular administration of betamethasone. By contrast, the cyclooxygenase inhibitor, indomethacin, tended to increase the NAP-1/IL-8 yield from PBMC in culture.

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Selected References

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  1. Arnett F. C., Edworthy S. M., Bloch D. A., McShane D. J., Fries J. F., Cooper N. S., Healey L. A., Kaplan S. R., Liang M. H., Luthra H. S. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988 Mar;31(3):315–324. doi: 10.1002/art.1780310302. [DOI] [PubMed] [Google Scholar]
  2. Baggiolini M., Schnyder J., Bretz U., Dewald B., Ruch W. Cellular mechanisms of proteinase release from inflammatory cells and the degradation of extracellular proteins. Ciba Found Symp. 1979;(75):105–121. doi: 10.1002/9780470720585.ch7. [DOI] [PubMed] [Google Scholar]
  3. Baggiolini M., Walz A., Kunkel S. L. Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. J Clin Invest. 1989 Oct;84(4):1045–1049. doi: 10.1172/JCI114265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bendtzen K., Petersen J., Halkjaer-Kristensen J., Ingemann-Hansen T. Interleukin-1-like activities in synovial fluids of patients with rheumatoid arthritis and traumatic synovitis. Rheumatol Int. 1985;5(2):79–82. doi: 10.1007/BF00270301. [DOI] [PubMed] [Google Scholar]
  5. Bevilacqua M. P., Pober J. S., Wheeler M. E., Cotran R. S., Gimbrone M. A., Jr Interleukin 1 acts on cultured human vascular endothelium to increase the adhesion of polymorphonuclear leukocytes, monocytes, and related leukocyte cell lines. J Clin Invest. 1985 Nov;76(5):2003–2011. doi: 10.1172/JCI112200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bomalaski J. S., Clark M. A., Zurier R. B. Enhanced phospholipase activity in peripheral blood monocytes from patients with rheumatoid arthritis. Arthritis Rheum. 1986 Mar;29(3):312–318. doi: 10.1002/art.1780290302. [DOI] [PubMed] [Google Scholar]
  7. Bomalaski J. S., Goldstein C. S., Dailey A. T., Douglas S. D., Zurier R. B. Uptake of fatty acids and their mobilization from phospholipids in cultured monocyte-macrophages from rheumatoid arthritis patients. Clin Immunol Immunopathol. 1986 May;39(2):198–212. doi: 10.1016/0090-1229(86)90084-x. [DOI] [PubMed] [Google Scholar]
  8. Burmester G. R., Dimitriu-Bona A., Waters S. J., Winchester R. J. Identification of three major synovial lining cell populations by monoclonal antibodies directed to Ia antigens and antigens associated with monocytes/macrophages and fibroblasts. Scand J Immunol. 1983 Jan;17(1):69–82. doi: 10.1111/j.1365-3083.1983.tb00767.x. [DOI] [PubMed] [Google Scholar]
  9. Bøyum A. Isolation of lymphocytes, granulocytes and macrophages. Scand J Immunol. 1976 Jun;Suppl 5:9–15. [PubMed] [Google Scholar]
  10. Colditz I. G., Zwahlen R. D., Baggiolini M. Neutrophil accumulation and plasma leakage induced in vivo by neutrophil-activating peptide-1. J Leukoc Biol. 1990 Aug;48(2):129–137. doi: 10.1002/jlb.48.2.129. [DOI] [PubMed] [Google Scholar]
  11. Colditz I., Zwahlen R., Dewald B., Baggiolini M. In vivo inflammatory activity of neutrophil-activating factor, a novel chemotactic peptide derived from human monocytes. Am J Pathol. 1989 Apr;134(4):755–760. [PMC free article] [PubMed] [Google Scholar]
  12. Cruchaud A., Despont J. P., Roth A., Dayer J. M. Phagocytosis, bactericidal capacity, and PGE2 production of monocytes in systemic lupus erythematosus and rheumatoid arthritis. Diagn Immunol. 1984;2(4):203–212. [PubMed] [Google Scholar]
  13. Dewald B., Baggiolini M. Evaluation of PAF antagonists using human neutrophils in a microtiter plate assay. Biochem Pharmacol. 1987 Aug 1;36(15):2505–2510. doi: 10.1016/0006-2952(87)90523-5. [DOI] [PubMed] [Google Scholar]
  14. Fernandez H. N., Henson P. M., Otani A., Hugli T. E. Chemotactic response to human C3a and C5a anaphylatoxins. I. Evaluation of C3a and C5a leukotaxis in vitro and under stimulated in vivo conditions. J Immunol. 1978 Jan;120(1):109–115. [PubMed] [Google Scholar]
  15. Firestein G. S., Zvaifler N. J. Peripheral blood and synovial fluid monocyte activation in inflammatory arthritis. I. A cytofluorographic study of monocyte differentiation antigens and class II antigens and their regulation by gamma-interferon. Arthritis Rheum. 1987 Aug;30(8):857–863. doi: 10.1002/art.1780300803. [DOI] [PubMed] [Google Scholar]
  16. Firestein G. S., Zvaifler N. J. Peripheral blood and synovial fluid monocyte activation in inflammatory arthritis. II. Low levels of synovial fluid and synovial tissue interferon suggest that gamma-interferon is not the primary macrophage activating factor. Arthritis Rheum. 1987 Aug;30(8):864–871. doi: 10.1002/art.1780300804. [DOI] [PubMed] [Google Scholar]
  17. Ford-Hutchinson A. W., Bray M. A., Doig M. V., Shipley M. E., Smith M. J. Leukotriene B, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes. Nature. 1980 Jul 17;286(5770):264–265. doi: 10.1038/286264a0. [DOI] [PubMed] [Google Scholar]
  18. Ghezzi P., Dinarello C. A. IL-1 induces IL-1. III. Specific inhibition of IL-1 production by IFN-gamma. J Immunol. 1988 Jun 15;140(12):4238–4244. [PubMed] [Google Scholar]
  19. Golds E. E., Mason P., Nyirkos P. Inflammatory cytokines induce synthesis and secretion of gro protein and a neutrophil chemotactic factor but not beta 2-microglobulin in human synovial cells and fibroblasts. Biochem J. 1989 Apr 15;259(2):585–588. doi: 10.1042/bj2590585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Gregory H., Young J., Schröder J. M., Mrowietz U., Christophers E. Structure determination of a human lymphocyte derived neutrophil activating peptide (LYNAP). Biochem Biophys Res Commun. 1988 Mar 15;151(2):883–890. doi: 10.1016/s0006-291x(88)80364-4. [DOI] [PubMed] [Google Scholar]
  21. Hasler F., Bluestein H. G., Zvaifler N. J., Epstein L. B. Analysis of the defects responsible for the impaired regulation of Epstein-Barr virus-induced B cell proliferation by rheumatoid arthritis lymphocytes. I. Diminished gamma interferon production in response to autologous stimulation. J Exp Med. 1983 Jan 1;157(1):173–188. doi: 10.1084/jem.157.1.173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Husby G., Williams R. C., Jr Immunohistochemical studies of interleukin-2 and gamma-interferon in rheumatoid arthritis. Arthritis Rheum. 1985 Feb;28(2):174–181. doi: 10.1002/art.1780280212. [DOI] [PubMed] [Google Scholar]
  23. Klareskog L., Forsum U., Malmnäs Tjernlund U. K., Kabelitz D., Wigren A. Appearance of anti-HLA-DR-reactive cells in normal and rheumatoid synovial tissue. Scand J Immunol. 1981 Aug;14(2):183–192. doi: 10.1111/j.1365-3083.1981.tb00198.x. [DOI] [PubMed] [Google Scholar]
  24. Le J., Vilcek J. Tumor necrosis factor and interleukin 1: cytokines with multiple overlapping biological activities. Lab Invest. 1987 Mar;56(3):234–248. [PubMed] [Google Scholar]
  25. Lindley I., Aschauer H., Seifert J. M., Lam C., Brunowsky W., Kownatzki E., Thelen M., Peveri P., Dewald B., von Tscharner V. Synthesis and expression in Escherichia coli of the gene encoding monocyte-derived neutrophil-activating factor: biological equivalence between natural and recombinant neutrophil-activating factor. Proc Natl Acad Sci U S A. 1988 Dec;85(23):9199–9203. doi: 10.1073/pnas.85.23.9199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Munthe E., Natvig J. B. Immunglobulin classes, subclasses and complexes of IgG rheumatoid factor in rheumatoid plasma cells. Clin Exp Immunol. 1972 Sep;12(1):55–70. [PMC free article] [PubMed] [Google Scholar]
  27. Murray H. W., Scavuzzo D., Jacobs J. L., Kaplan M. H., Libby D. M., Schindler J., Roberts R. B. In vitro and in vivo activation of human mononuclear phagocytes by interferon-gamma. Studies with normal and AIDS monocytes. J Immunol. 1987 Apr 15;138(8):2457–2462. [PubMed] [Google Scholar]
  28. Peveri P., Walz A., Dewald B., Baggiolini M. A novel neutrophil-activating factor produced by human mononuclear phagocytes. J Exp Med. 1988 May 1;167(5):1547–1559. doi: 10.1084/jem.167.5.1547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Pohlman T. H., Stanness K. A., Beatty P. G., Ochs H. D., Harlan J. M. An endothelial cell surface factor(s) induced in vitro by lipopolysaccharide, interleukin 1, and tumor necrosis factor-alpha increases neutrophil adherence by a CDw18-dependent mechanism. J Immunol. 1986 Jun 15;136(12):4548–4553. [PubMed] [Google Scholar]
  30. Schröder J. M., Christophers E. Secretion of novel and homologous neutrophil-activating peptides by LPS-stimulated human endothelial cells. J Immunol. 1989 Jan 1;142(1):244–251. [PubMed] [Google Scholar]
  31. Seitz M., Deimann W., Gram N., Hunstein W., Gemsa D. Characterization of blood mononuclear cells of rheumatoid arthritis patients. I. Depressed lymphocyte proliferation and enhanced prostanoid release from monocytes. Clin Immunol Immunopathol. 1982 Dec;25(3):405–416. doi: 10.1016/0090-1229(82)90205-7. [DOI] [PubMed] [Google Scholar]
  32. Seitz M., Hunstein W. Enhanced prostanoid release from monocytes of patients with rheumatoid arthritis and active systemic lupus erythematosus. Ann Rheum Dis. 1985 Jul;44(7):438–445. doi: 10.1136/ard.44.7.438. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Seitz M., Napierski I., Augustin R., Hunstein W., Kirchner H. Reduced production of interferon alpha and interferon gamma in leukocyte cultures from patients with active rheumatoid arthritis. Scand J Rheumatol. 1987;16(4):257–262. doi: 10.3109/03009748709102926. [DOI] [PubMed] [Google Scholar]
  34. Shalaby M. R., Aggarwal B. B., Rinderknecht E., Svedersky L. P., Finkle B. S., Palladino M. A., Jr Activation of human polymorphonuclear neutrophil functions by interferon-gamma and tumor necrosis factors. J Immunol. 1985 Sep;135(3):2069–2073. [PubMed] [Google Scholar]
  35. Smiley J. D., Sachs C., Ziff M. In vitro synthesis of immunoglobulin by rheumatoid synovial membrane. J Clin Invest. 1968 Mar;47(3):624–632. doi: 10.1172/JCI105758. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Stolzenburg T., Binz H., Fontana A., Felder M., Wagenhaeuser F. J. Impaired mitogen-induced interferon-gamma production in rheumatoid arthritis and related diseases. Scand J Immunol. 1988 Jan;27(1):73–81. doi: 10.1111/j.1365-3083.1988.tb02324.x. [DOI] [PubMed] [Google Scholar]
  37. Strieter R. M., Kunkel S. L., Showell H. J., Marks R. M. Monokine-induced gene expression of a human endothelial cell-derived neutrophil chemotactic factor. Biochem Biophys Res Commun. 1988 Nov 15;156(3):1340–1345. doi: 10.1016/s0006-291x(88)80779-4. [DOI] [PubMed] [Google Scholar]
  38. Strieter R. M., Phan S. H., Showell H. J., Remick D. G., Lynch J. P., Genord M., Raiford C., Eskandari M., Marks R. M., Kunkel S. L. Monokine-induced neutrophil chemotactic factor gene expression in human fibroblasts. J Biol Chem. 1989 Jun 25;264(18):10621–10626. [PubMed] [Google Scholar]
  39. Waalen K., Duff G. W., Førre O., Dickens E., Kvarnes L., Nuki G. Interleukin 1 activity produced by human rheumatoid and normal dendritic cells. Scand J Immunol. 1986 Mar;23(3):365–371. doi: 10.1111/j.1365-3083.1986.tb01977.x. [DOI] [PubMed] [Google Scholar]
  40. Walz A., Peveri P., Aschauer H., Baggiolini M. Purification and amino acid sequencing of NAF, a novel neutrophil-activating factor produced by monocytes. Biochem Biophys Res Commun. 1987 Dec 16;149(2):755–761. doi: 10.1016/0006-291x(87)90432-3. [DOI] [PubMed] [Google Scholar]
  41. Watson M. L., Westwick J., Fincham N. J., Camp R. D. Elevation of PMN cytosolic free calcium and locomotion stimulated by novel peptides from IL-1-treated human synovial cell cultures. Biochem Biophys Res Commun. 1988 Sep 30;155(3):1154–1160. doi: 10.1016/s0006-291x(88)81261-0. [DOI] [PubMed] [Google Scholar]
  42. Yoshimura T., Matsushima K., Tanaka S., Robinson E. A., Appella E., Oppenheim J. J., Leonard E. J. Purification of a human monocyte-derived neutrophil chemotactic factor that has peptide sequence similarity to other host defense cytokines. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9233–9237. doi: 10.1073/pnas.84.24.9233. [DOI] [PMC free article] [PubMed] [Google Scholar]

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