Springer Nature is making Coronavirus research free. View research | View latest news | Sign up for updates

Occurrence of interleukin-1 in human synovial fluid: detection by RIA, bioassay and presence of bioassay-inhibiting factors

  • 20 Accesses

  • 50 Citations


Synovial fluid (SF) from patients with osteoarthritis (OA), rheumatoid arthritis (RA), and various other arthridites was analyzed to assess the prevalence of interleukin-1 (IL-1) using both radioimmunoassay competitive inhibition specific for the beta form of IL-1 and the D10.G4.1 cell line bioassay which measures both alpha and beta forms of IL-1. Using radioimmunoassay competitive inhibition, IL-1β was found in 45% and 60% of individual samples from patients with OA and RA respectively. When RA and OA SF were examined in sequentially obtained samples, IL-1β occurred in one or more samples from 8 of 10 patients studied, suggesting the probability that it can be produced at some time in SF by all patients with these conditions. No correlation between SF leukocyte counts and the occurrence of IL-1β was noted and no effect of antiinflammatory drug treatment on the prevalence of IL-1β was found. When tested for the presence of IL-1 by the D10.G4-1 cell line, 66% and 50% of RA and OA patients respectively were found to contain IL-1. These were not in total concordance with results obtained by RIA. Of all SF tested, seven were negative by RIA but positive by D10.G4.1 and these are considered to contain IL-1α. Seven samples which were RIA positive and D10.G4.1 negative were tested for their ability to inhibit IL-1 responses in the bioassay. Five of these contained inhibitor and one markedly enhanced the proliferative response of D10.G4.1 to a known amount of IL-1. The inhibitors and the non-IL-1 enhancing factor have yet to be characterized.

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


  1. 1.

    Fontana A, Hengartner H, Weber E, Fehr K, Grob PJ, Cohen G (1982) Interleukin-1 activity in the synovial fluid of patients with rheumatoid arthritis. Rheumatol Int 2:49–53

  2. 2.

    Wood DD, Ihrie RJ, Dinarello CA, Cohen PL (1983) Isolation of an interleukin-1-like factor from human joint effusions. Arthritis Rheum 26:975–983

  3. 3.

    Nouri AME, Panayi GS, Goodman SM (1984) Cytokines and the chronic inflammation of rheumatic disease. I. The presence of IL-1 in synovial fluids. Clin Exp Immunol 55:295–302

  4. 4.

    Miossec P, Dinarello CA, Ziff M (1986) Interleukin-1 lymphocyte chemotactic activity in rheumatoid arthritis synovial fluid. Arthritis Rheum 29:461–470

  5. 5.

    Mizel SP, Dayer J-M, Krane SM, Morgenhagen SE (1984) Stimulation of rheumatoid synovial cell collagenase and prostaglandin production by partially purified lymphocyteactivity factor (interleukin-1). Proc Natl Acad Sci USA 78:2474–2477

  6. 6.

    DiPasquale G, Caccese R, Pasternak R, Conaty J, Hubbs S, Perry K (1986) Proteoglycan- and collagen-degrading enzymes from human interleukin-1-stimulated chondrocytes from several species: Proteoglycanase and collagenase inhibitors as potentially new disease-modifying antiarthritic agents. Proc Soc Exp Biol Med 183:262–267

  7. 7.

    Gowan M, Wood DD, Ihrie EJ, Meats JE, Russell GG (1984) Stimulation by human interleukin-1 of cartilage breakdown and production of collagenase and proteoglycanase by human chondrocytes but not by human osteoblasts in vitro. Biochem Biophys Acta 797:186–193

  8. 8.

    Campbell IK, Roughley PJ, Mort JS (1986) The action of human articular-cartilage metalloproteinase on proteoglycan and link protein: similarities between products of degradation in situ and in vitro. Biochem J 237:117–192

  9. 9.

    Pettipher ER, Higgs GA, Henderson B (1986) Interleukin-1 induces leukocyte infiltration and cartilage proteoglycan degradation in the synovial joint. Proc Natl Acad Sci USA 83:8749–8753

  10. 10.

    Richardson HJ, Elford PR, Sharrard RM, Meats JE, Russell RGG (1985) Modulation of connective tissue metabolism by partially purified human interleukin-1. Cell Immunol 90:41–51

  11. 11.

    Vogel SN, Douches SD, Kaugman EN, Neta R (1987) Induction of colony stimulating factor in vivo by recombinant interleukin-1 and recombinant tumor necrosis factor. J Immunol 138:2143–2148

  12. 12.

    Lotz M, Carson DA, Vaughan JH (1986) Characterization of interleukin-1 inhibitors in rheumatoid synovial fluid. Arthritis Rheum 29 (suppl):538 (abstr)

  13. 13.

    Liao Z, Haimovitz A, Chen Y, Chan J, Rosenstreich DL (1985) Characterization of a human interleukin-1 inhibitor. J Immunol 134:3882–3886

  14. 14.

    Dinarello CA, Rosenwasser LJ, Wolff SM (1981) Demonstration of a circulating suppressor factor of thymocyte proliferation during endotoxin fever in humans. J Immunol 127:2517–2519

  15. 15.

    Muchmore AV, Shifrin S, Decker J (1987) In vitro evidence that carbohydrate moieties derived from uromodulin, an 85 000 Dalton immunosuppressive glycoprotein isolated from human pregnancy urine, are immunosuppressive in the absence of intact protein. J Immunol 138:2547–2553

  16. 16.

    Arend WP, Joslin FG, Massoni RJ (1985) Effects of immune complexes on production by human monocytes of interleukin-1 or an interleukin-1 inhibitor. J Immunol 134:3868–3875

  17. 17.

    Kaye J, Janeway CA Jr (1984) The alpha and beta subunits of a murine T cell antigen/Ia receptor have a molecular weight of 31 000 in the absence of W-linked glycosylation. J Immunol 133:2291–2293

  18. 18.

    Ropes WM, Bennett GA, Cobbs S, Jacox R, Jessar RA (1958) 1958 revision of diagnostic criteria for rheumatoid arthritis. Bull Rheum Dis 9:175–176

  19. 19.

    Gillis S, Mizel SB (1981) T cell lymphoma model for the analysis of interleukin-1-mediated T cell activation. Proc Natl Acad Sci USA 78:1133–1137

  20. 20.

    Bocchieri MH, Smith JB, Smith JB Jr, Staruch MJ, Wood DD (1985) Functional consequences of perceived interleukin deficiencies? Analysis employing NZB × C58 recombinant inbred mice. Clin Exp Immunol 62:622–629

  21. 21.

    Wilkins JA, Warrington RJ, Sigurdson SL, Rutherford WJ (1983) The demonstration of an interleukin-2 like activity in the synovial fluids of rheumatoid arthritis patients. J Rheumatol 10:109–113

  22. 22.

    Lenim G, Warnatz H (1986) Evidence for enhanced interleukin-2 (IL-2) secretion and IL-2 receptor presentation by synovial fluid lymphocytes in rheumatoid arthritis. Clin Exp Immunol 64:71–79

  23. 23.

    Miossec P, Kashiwado T, Ziff M (1987) Inhibitor of interleukin-2 in rheumatoid arthritis synovial fluid. Arthritis Rheum 30:121–129

  24. 24.

    Knoblock C, Schlesier M, Drager R, Gartner M, Peter HH (1985) Quantitative absorption of IL-2 by peripheral blood and synovial fluid lymphocytes from patients with rheumatoid arthritis. Rheumatol Int 5:133–139

  25. 25.

    Miyasaka N, Sato K, Goto M, Sasano M, Natsuyama M, Inoue K, Nishioka K (1988) Augmented interleukin-1 production and HLA-DR expression in the synovium of rheumatoid patients: possible involvement in joint destruction. Arthritis Rheum 31:480–486

  26. 26.

    Durum SK, Schmidt JA, Oppenheim JJ (1985) Interleukin-1: an immunological perspective. Annu Rev Immunol 3:263–287

  27. 27.

    Williamson DJ, Begley CG, Vadas MA, Metcalf D (1988) The detection and initial characterization of colony-stimulating factors in synovial fluid. Clin Exp Immunol 72:67–73

Download references

Author information

Correspondence to J. B. Smith.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Smith, J.B., Bocchieri, M.H., Sherbin-Allen, L. et al. Occurrence of interleukin-1 in human synovial fluid: detection by RIA, bioassay and presence of bioassay-inhibiting factors. Rheumatol Int 9, 53–58 (1989).

Download citation

Key words

  • Rheumatoid arthritis
  • Osteoarthritis
  • Interleukin-1
  • Synovial fluid
  • Radioimmunoassay