Synovial fluid from patients with rheumatoid arthritis contains a unique inhibitor of interleukin 1 alpha.
OBJECTIVE
To partially purify and characterize a specific inhibitor of interleukin 1 alpha (IL-1 alpha) activity from synovial fluids (SF) of patients with rheumatoid arthritis.


METHODS
SF inhibitor of IL-1 alpha (SFI alpha) was partially purified by ammonium sulfate precipitation, gel filtration, anion exchange chromatography, and chromatofocusing. Specificity of inhibition of IL-1 alpha activity was tested in T lymphocyte proliferation assays. The mechanism of this inhibition was investigated by binding assays and mobility shift on gel filtration.


RESULTS
The SFI alpha inhibited all in vitro activities of IL-1 alpha tested, but did not inhibit activities of IL-1 beta or IL-2. Inhibitor activity was not diminished by neutralizing antibodies against the IL-1 receptor antagonist, and was not removed by immunoadsorption with antibodies against IL-1 receptors. It was not depleted by monoclonal antibodies against human IgG subclasses, IgA, or IgM. The SFI alpha specifically inhibited binding of IL-1 alpha to cell surface receptors, and appeared to form a high molecular weight complex with IL-1 alpha.


CONCLUSIONS
SFI alpha appeared to block biological activities of IL-1 alpha by specific binding to this cytokine, thereby preventing receptor occupancy. The SFI alpha did not appear to be related to previously described inhibitors of IL-1.
Higgins
G C
GC
Department of Pediatrics, University of Tennessee, Memphis 38103, USA.
Postlethwaite
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AE
D000818:Animals; D000906:Antibodies / Q000032:analysis; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007118:Immunoassay; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D017472:Receptors, Interleukin-1 / Q000737:chemistry; D013582:Synovial Fluid / Q000737:chemistry*
D000906:Antibodies; D007375:Interleukin-1; D017472:Receptors, Interleukin-1