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 a lso been shown to have a crucial role in the pathogenesis of acute gou ty arthritis, Thus, we investigate the pathophysiological role of IL-8 in an experimental model of acute gout, monosodium urate (MSU) crysta l-induced arthritis in rabbits, The injection of MSU crystals into kne e joints caused a marked swelling: of joints, Concomitantly, the infil tration of leukocytes, mostly neutrophils, was observed in synovial me mbrane and synovial fluids, The injection of MSU crystals also induced an elevation in synovial fluid IL-8 levels preceding neutrophil infil tration into synovial fluids, without an accompanying increase in plas ma IL-8 levels, Immunoreactive IL-8 protein was detected in synovial l ining cells at 12-24 h after the injection, IL-8 protein was also obse rved in infiltrated leukocytes in synovium as early as 3-24 h after th e injection, Finally, the intraarticular injection of a neutralizing a nti-IL-8 antibody significantly attenuated the crystal-induced joint s welling that occurred at 12 h, and neutrophil infiltration into arthri tic joints at 12 and 24 h after the induction, These results provide e vidence on the pathogenic roles of locally produced IL-8 in MSU crysta l-induced gouty arthritis.