Experimental arthritis induced by continuous infusion of IL-8 into rabbit knee joints

Abstract

SUMMARY To determine the roles of IL‐8 in inflammatory synovitis. examination was made of the results of continuously injecting human recombinant IL‐8 into the knee joints of New Zealand white rabbits. Recombinant human lL‐8 was infused continuously into the joint cavity at 75 ng/h for 14 days by a polypropylene catheter connected to a mini‐osmotic pump implanted in each rabbit. Infiltration of inflammatory cells into joint cavity and histopathological changes in synovial tissue were examined at 7 and 14 days following the start of infusion. The continuous infusion of IL‐8 for 14days led to severe arthritis characterized by apparent erythema and joint pain, the accumulation of leucocytes, infiltration of mononuclear cells in synovial tissue, and marked hypervascularization in the synovial lining layer. IL‐8 may be a factor which can contribute to the inflammatory process of chronic arthritis by mediating leucocyte recruitment and hypervascularization in inflamed joints.

Protective role of IFN-γ in collagen-induced arthritis conferred by inhibition of mycobacteria-induced granulocyte chemotactic protein-2 production

“…Strong evidence for the importance of IL-8 in the pathogenesis of RA has been provided by Kraan et al [10]: IL-8 was not detectable in synovial extracts of healthy, control individuals, was detectable in clinically uninvolved joints of RA patients, and increased in clinically involved joints of RA patients. Moreover, IL-8 was found capable of inducing synovial inflammation in an animal model [15].…”

“…In RA, the development of clinical signs of synovial inflammation correlates with increased local synthesis of the chemokine IL-8 (CXCL8) [9 -13], the prototype of human CXC chemokines that affect mainly neutrophil migration. IL-8 is produced constitutively by macrophages in the synovial compartment [14], and continuous infusion of IL-8 is capable of inducing severe arthritis into rabbit knee joints [15]. In mice, IL-8 has not been described, but the major neutrophilattracting chemokine is granulocyte chemotactic protein-2 (GCP-2), generally considered as the functional equivalent of IL-8 in humans [16,17].…”

Anti-inflammatory activities of Chinese herbal medicine sinomenine and Liang Miao San on tumor necrosis factor-α-activated human fibroblast-like synoviocytes in rheumatoid arthritis

“…Inflammatory chemokine CXCL8 is able to attract immune cells, especially neutrophils, into the inflammatory site (Vergunst et al, 2005). Continuous infusion of human recombinant CXCL8 into rabbit knee joints can lead to the accumulation of leucocytes, infiltration of mononuclear cells into synovial tissue and marked hypervascularization in the synovial lining layer (Endo et al, 1994). A neutralizing antibody to CXCL8 can prevent neutrophil infiltration into lipopolysaccharide/IL-1␤-induced arthritis and attenuate monosodium urate crystal-induced leukocyte infiltration into knee joints in rabbit (Harada et al, 1994;Nishimura et al, 1997).…”

Activation of human fibroblast-like synoviocytes by uric acid crystals in rheumatoid arthritis

“…35 Continuous infusion of human recombinant CXCL8 into rabbit knee joints can lead to the accumulation of leukocytes, the infiltration of mononuclear cells into synovial tissue and marked hypervascularization in the synovial lining layer. 36 A neutralizing antibody to CXCL8 can prevent neutrophil infiltration in lipopolysaccharide/IL-1-induced arthritis and attenuate monosodium urate crystal-induced Figure 3 The combined effects of monosodium urate crystals and TNF-a on the induction of IL-6, CXCL8 and MMP-1 release from FLS. Control and RA-FLS were cultured with or without monosodium urate crystals (100-200 mg/ml) and TNF-a (10 ng/ml) alone or in combination for 48 h. Release of (a) IL-6, (b) CXCL8 and (c) MMP-1 were determined by CBA or ELISA.…”