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.
Endo
H
H
Department of Internal Medicine, Kitasato University School of Medicine, Kanagawa, Japan.
Akahoshi
T
T
Takagishi
K
K
Kashiwazaki
S
S
Matsushima
K
K
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