Elevation of interleukin-8 (IL-8) levels in joint fluids of patients with rheumatoid arthritis and the induction by IL-8 of leukocyte infiltration and synovitis in rabbit joints.
Increased amounts of interleukin-8 (IL-8) were detected in synovial fluids of patients with active rheumatoid arthritis (RA) by radioimmunoassay (RIA). The concentration of IL-8 correlated directly with the number of infiltrating neutrophils in synovial fluids. To elucidate the role of IL-8 in neutrophil accumulation at the site of synovitis, the in vivo effects of intraarticular injection of recombinant IL-8 (rIL-8) on leukocytes infiltration into the joint space and synovium were examined. Following a single injection of rIL-8 into the knee joint space of rabbits, redness of the joint and limp became apparent after 4 h and were associated with the rapid infiltration of neutrophilic leukocytes into the joint space and synovial tissues. These effects were time dependent, first becoming evident at 1 h and reaching a plateau in 4 h, and also dose dependent, with a minimal effect being elicited by 100 ng per joint. Although neutrophils were present in the greatest number at 4 h, subsequently mononuclear cells accumulated and became apparent in considerable number after 8 h. Synovial lining cells became ovoid, pleomorphic, and multilayered at 24 h. IL-8 had no effect on the breakdown of proteoglycan of articular cartilage. Based on these findings, IL-8 released from monocytes and synovial cells may be an important contributor to leukocyte accumulation and inflammatory events in the joints of RA.
Department of Internal Medicine, Kitasato University School of Medicine, Kanagawa, Japan.
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H
Endo
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T
Akahoshi
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K
Takagishi
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S
Kashiwazaki
K
K
Matsushima
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism* / Q000494:pharmacology; D007596:Joints / Q000378:metabolism*; D007962:Leukocytes / Q000502:physiology; D010003:Osteoarthritis / Q000378:metabolism; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D013582:Synovial Fluid / Q000378:metabolism*; D013585:Synovitis / Q000139:chemically induced* / Q000473:pathology
D006025:Glycosaminoglycans; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D011994:Recombinant Proteins