Attenuation of monosodium urate crystal-induced arthritis in rabbits by a neutralizing antibody against interleukin-8

Accumulating evidence implicates interleukin-8 (IL-8) as an essential mediator in neutrophil-mediated acute inflammation, Neutrophils have also been shown to have a crucial role in the pathogenesis of acute gouty arthritis, Thus, we investigate the pathophysiological role of IL-8 in an experimental model of acute gout, monosodium urate (MSU) crystal-induced arthritis in rabbits, The injection of MSU crystals into knee joints caused a marked swelling: of joints, Concomitantly, the infiltration of leukocytes, mostly neutrophils, was observed in synovial membrane and synovial fluids, The injection of MSU crystals also induced an elevation in synovial fluid IL-8 levels preceding neutrophil infiltration into synovial fluids, without an accompanying increase in plasma IL-8 levels, Immunoreactive IL-8 protein was detected in synovial lining cells at 12-24 h after the injection, IL-8 protein was also observed in infiltrated leukocytes in synovium as early as 3-24 h after the injection, Finally, the intraarticular injection of a neutralizing anti-IL-8 antibody significantly attenuated the crystal-induced joint swelling that occurred at 12 h, and neutrophil infiltration into arthritic joints at 12 and 24 h after the induction, These results provide evidence on the pathogenic roles of locally produced IL-8 in MSU crystal-induced gouty arthritis.