Summary
The content of interleukin-8 (IL-8) in the synovial fluid and its production by blood and synovial fluid mononuclear cells (PBMC and SFMC) was compared in rheumatoid arthritis (RA) and various other inflammatory rheumatic disorders. The study included 125 patients and 20 healthy individuals. The highest concentrations of IL-8 were found in the synovial fluids and culture supernatants of PBMC and SFMC from patients with seropositive RA. Only PBMC from seropositive patients, and not from other rheumatic diseases, exhibited significant spontaneous release of IL-8 that correlated with serum IgM rheumatoid factor titers. Gold sodium thiomalate (GST) and methotrexate (MTX) inhibited the spontaneous and stimulated IL-8 production by PBMC by 55–86% at 50 and 10 μg/ml, respectively. Two main conclusions were drawn: (1) rheumatoid factors appeared to be a major cause of enhanced IL-8 production in seropositive RA, and (2) inhibition of IL-8-mediated neutrophil migration and activation could be part of the mechanism of action of GST and MTX.
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Ryan GB (1967) The origin and sequence of the cells found in the acute inflammatory response. Aust J Exp Biol Med Sci 45:149–162
Matsushima K, Oppenheim JJ (1989) Interleukin 8 and MCAF: novel inflammatory cytokines inducible by IL 1 and TNF. Cytokine 1:2–13
Baggiolini M, Walz A, Kunkel SL (1989) Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. J Clin Invest 84:1045–1049
Watson ML, Westwick J, Fincham NJ, Camp RD (1988) Elevation of PMN cytosolic free calcium and locomotion stimulated by novel peptides from IL-1-treated human synovial cell cultures. Biochem Biophys Res Commun 155:1154–1160
Golds EE, Mason P, Nyirkos P (1989) Inflammatory cytokines induce synthesis and secretion of gro protein and a neutrophil chemotactic factor but not β2-microglobulin in human synovial cells and fibroblasts. Biochem J 259:585–588
Brennan FM, Zachariae COC, Chantry D, Larsen CG, Turner M, Maini RN, Matsushima K, Feldmann M (1990) Detection of interleukin 8 biological activity in synovial fluids from patients with rheumatoid arthritis and production of interleukin 8 mRNA by isolated synovial cells. Eur J Immunol 20:2141–2144
Seitz M, Dewald B, Gerber N, Baggiolini M (1991) Enhanced production of neutrophil-activating peptide-1/interleukin-8 in rheumatoid arthritis. J Clin Invest 87:463–469
Fernandez HN, Henson PM, Otani A, Hugli TE (1978) Chemotactic response to human C3a and C5a anaphylatoxins, I. Evaluation of C3a and C5a leukotaxis in vitro and under simulated in vivo conditions. J Immunol 120:109–115
Lee TC, Snyder F (1985) Function, metabolism and regulation of platelet activating factor and related ether lipids. In: Kuo JF (ed) Phospholipids and cellular regulation. CRC, Boca Raton, pp 1–39
Ford Hutchinson AW, Bray MA, Doig MV, Shipley ME, Smith MJ (1980) Leukotriene B, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes. Nature 286:264–265
Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS et al. (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324
Boyum A (1976) Isolation of lymphocytes, granulocytes and macrophages. Scand J Immunol 5:9–15
Koski JR, Poplak DG, Blaese RMA (1976) Nonspecific esterase stain for the identification of monocytes and macrophages. Academic Press, New York, p 359
Seitz M, Hunstein W (1985) Enhanced prostanoid release from monocytes of patients with rheumatoid arthritis and active systemic lupus erythematosus. Ann Rheum Dis 44:438–445
Bazzoni F, Cassatella MA, Rossi F, Ceska M, Dewald B, Baggiolini M (1991) Phagocytosing neutrophils produce and release high amounts of the neutrophil-activating peptide 1/interleukin 8. J Exp Med 173:771–774
Lindley I, Aschauer H, Seifert JM, Lam C, Brunowsky W, Kownatzki E, Thelen M, Peveri P, Dewald B, Tscharner V von, Walz A, Baggiolini M (1988) 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 USA 85:9199–9203
Ugai K, Ziff M, Lipsky PE (1979) Gold-induced changes in the morphology and functional capabilities of human monocytes. Arthritis Rheum 22:1352–1360
Salmeron G, Lipsky PE (1982) Modulation of human immune responsiveness in vitro by auranofin. J Rheumatol [Suppl] 8:25–31
Littman BH, Schwartz P (1982) Gold inhibition of the production of the second complement component by lymphokine-stimulated human monocytes. Arthritis Rheum 25:288–296
Ghadially FN, Oryschak AF, Mitchell DM (1976) Ultrastructural changes produced in rheumatoid synovial membrane by chrysotherapy. Ann Rheum Dis 35:67–72
Vernon Roberts B, Dore JL, Jessop JD, Henderson WJ (1976) Selective concentration and localization of gold in macrophages of synovial and other tissues during and after chrysotherapy in rheumatoid patients. Ann Rheum Dis 35:477–486
Nakamura H, Igarashi M (1977) Localization of gold in synovial membrane of rheumatoid arthritis treated with sodium aurothiomalate: Studies by electron microscope and electron probe x-ray microanalysis. Ann Rheum Dis 36:209–215
Jessop JD, Vernon Roberts B, Harris J (1973) Effects of gold salts and prednisolone on inflammatory cells I. Phagocytic activity of macrophages and polymorphs in inflammatory exudates studied by a “skin-window” technique in rheumatoid and control patients. Ann Rheum Dis 32:294–300
Gottlieb NL, Smith PM, Smith EM (1972) Tissue gold concentration in a rheumatoid arthritic receiving chrysotherapy. Arthritis Rheum 15:16–22
Kremer JM, Galivan J, Streckfuss A, Kamen B (1986) Methotrexate metabolism analysis in blood and liver of rheumatoid arthritis patients. Association with hepatic folate deficiency and formation of polyglutamates. Arthritis Rheum 29:832–835
Strieter RM, Kunkel SL, Showell HJ, Remick GD, Phan SH, Ward PA, Marks RM (1989) Endothelial cell gene expression of a neutrophil chemotactic factor by TNF, IL-1 and LPS. Science 243:1467–1469
Schroder JM, Christophers E (1989) Secretion of novel and homologous neutrophil-activating peptides by LPS-stimulated human endothelial cells. J Immunol 142:244–251
Sica A, Matsushima K, Van Damme J, Wang JM, Polentarutti N, Dejana E, Colotta F, Mantovani A (1990) IL-1 transcriptionally activates the neutrophil chemotactic factor/IL-8 gene in endothelial cells. Immunology 69:548–553
Van Damme J, Bunning RAD, Conings R, Graham R, Russell G, Opdenakker G (1990) Characterization of granulocyte chemotactic activity from human cytokine-stimulated chondrocytes as interleukin 8. Cytokine 2:106–111
Klickstein LB, Shapleigh C, Goetzl EJ (1980) Lipoxygenation of arachidonic acid as a source of polymorphonuclear leukocyte chemotactic factors in synovial fluid and tissue in rheumatoid arthritis and spondyloarthritis. J Clin Invest 66:1166–1170
Ward PA, Zvaifler NJ (1971) Complement-derived leukotactic factors in inflammatory synovial fluids of humans. J Clin Invest 50:606–616
Forestier J (1935) Rheumatoid arthritis and its treatment by gold salts. J Lab Clin Med 20:827–840
Penneys NS, McCreary S, Gottlieb NL (1976) Intracellular distribution of radiogold: Localization to large granule membranes. Arthritis Rheum 19:927–932
Gottlieb NL (1985) Gold compounds. In: Kelley WN, Harris ED Jr, Ruddy S, Sledge CB (eds). Saunders, Philadelphia pp 789–809
Petersen J, Bendtzen K (1983) Immunosuppressive actions of gold salts. Scand J Rheumatol [Suppl] 51:28–35
Ho PP, Young AL, Southard GL (1978) Methyl ester of N-formylmethionyl-leucyl-phenylalanine: Chemotactic responses of human blood monocytes and inhibition of gold compounds. Arthritis Rheum 21:133–136
Vernon Roberts B, Jessop JD, Dore J (1973) Effects of gold salts and prednisolone on inflammatory cells II. Suppression of inflammation and phagocytosis in the rat. Ann Rheum Dis 32:301–307
Littman BH, Hall RE (1985) Effects of gold sodium thiomalate on functional correlates of human monocyte maturation. Arthritis Rheum 28:1384–1392
Spalding DM, Darby WL, Heck LW (1986) Alterations in macrophage collagenase secretion induced by gold sodium thiomalate. Arthritis Rheum 29:75–81
Ennis RS, Granda JL, Posner AS (1968) Effect of gold salts and other drugs on the release and activity of lysosomal hydrolases. Arthritis Rheum 11:756–764
Schultz DR, Volanakis JE, Arnold PI, Gottlieb NL, Sakai K, Stroud RM (1974) Inactivation of C1 in rheumatoid synovial fluid, purfied C1 and C1 esterase, by gold compounds. Clin Exp Immunol 17:395–406
Burkhardt D, Stephens RW, Ghosh P, Taylor TK (1978) Inhibition of synovial fluid lysosomal glycosidases by anti-arthritic gold preparations. Agents Actions 8:251–257
Sanders KM, Carlson PL, Littman BH (1987) Effects of gold sodium thiomalate on interferon stimulation of C2 synthesis and HLA-DR expression by human monocytes. Arthritis Rheum 30:1032–1039
Drakes ML, Harth M, Galsworthy SB, McCain GA (1987) Effects of gold on the production of and response to human interleukin-1. J Rheumatol 14:1123–1127
Remvig L, Enk C, Bligaard N (1988) Effect of auranofin and sodium aurothiomalate on interleukin-1 production from human monocytes in vitro. Scand J Rheumatol 17:255–262
Danis VA, Kulesz AJ, Nelson DS, Brooks PM (1990) The effect of gold sodium thiomalate and auranofin on lipopolysaccharide-induced interleukin-1 production by blood monocytes in vitro: variation in healthy subjects and patients with arthritis. Clin Exp Immunol 79:335–340
Furst DE, Kremer JM (1988) Methotrexate in rheumatoid arthritis. Arthritis Rheum 31:305–314
Weinblatt ME, Coblyn JS, Fox DA, Fraser PA, Holdsworth D, Glass DN, Trentham DE (1985) Efficacy of low-dose methotrexate in rheumatoid arthritis. N Engl J Med 312:818–822
Kremer JM, Rynes RI, Bartholomew LE (1987) Severe flare of rheumatoid arthritis after discontinuation of long-term methotrexate therapy. Double-blind study. Am J Med 82:781–786
Cream JJ, Pole DS (1980) The effect of methotrexate and hydroxyurea on neutrophil chemotaxis. Br J Dermatol 102:557–563
Harris ED Jr (1985) Pathogenesis of rheumatoid arthritis. Text-book of Rheumatology. In: Kelley WN, Harris ED Jr, Ruddy S, Sledge CB (eds) Saunders, Philadelphia, pp 890–893
Sticherling M, Bornscheuer E, Schröder J-M, Christophers E (1991) Localization of neutrophil-activating peptide-1/interleukin-8-immunoreactivity in normal and psoriatic skin. J Invest Dermatol 96:26–30
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Seitz, M., Dewald, B., Ceska, M. et al. Interleukin-8 in inflammatory rheumatic diseases: synovial fluid levels, relation to rheumatoid factors, production by mononuclear cells, and effects of gold sodium thiomalate and methotrexate. Rheumatol Int 12, 159–164 (1992). https://doi.org/10.1007/BF00274936
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DOI: https://doi.org/10.1007/BF00274936