INVOLVEMENT OF INTERLEUKIN-8 IN DIALYSIS-RELATED ARTHRITIS

To elucidate the role of interleukin (IL)-8, a chemotactic factor for neutrophils, in dialysis-related arthritis (DRA) of patients on long-t erm hemodialysis, the concentration of IL-8 was measured in the synovi al fluids of DRA patients with acute arthralgia and joint swelling, an d was compared with those in patients with rheumatoid arthritis (RA) a nd patients with osteoarthritis (OA). We noted a marked elevation of I L-8 in the joint fluids oi patients with DRA and RA as compared with O A. Furthermore. to determine the role of IL-8 in synovitis, we examine d the in vile effect of intra-articular injection of human recombinant IL-8 on leukocyte infiltration into the joint space of rabbits. A sin gle injection of IL-8 to the joints of rabbits induced rapid infiltrat ion of neutrophils into the joint space and synovial tissues, which re ached a maximum in four hours. The oral administration of indometacin farnesil (a prodrug that is converted to indomethacin after intestinal absorption) before the injection of IL-8 alleviated the infiltration of neutrophils. When human synovial cells were incubated with tumor ne crosis factor (TNF)-alpha, the expression of IL-8 mRNA and IL-8 produc tion in the cultured synovial cells were increased. The TNF-alpha-stim ulated expression of IL-8 mRNA and IL-8 production in the cultured syn ovial cells were markedly inhibited by dexamethasone. In conclusion, I L-8 levels were markedly elevated in the joint fluids of patients with DRA. Interleukin-8 released from synovial cells may be an important f actor to induce acute inflammation in DRA. Dexamethasone and indometha cin may be effective for DRA by inhibiting the production and chemotac tic actions of IL-8, respectively.