Modulation of inflammation by kininogen deficiency in a rat model of inflammatory arthritis.

To compare inflammatory peripheral arthritis in wild‐type and high molecular weight kininogen (HK)–deficient rats, both on the genetically susceptible Lewis background.By backcrossing Brown‐Norway HK‐deficient rats with Lewis rats for 6 generations, 2 new strains were produced, wild‐type F6 and HK‐deficient F6, each with a 98.5% Lewis genome. Inflammatory arthritis was induced by intraperitoneal injection of peptidoglycan–polysaccharide (PG‐PS), and the clinical, histopathologic, and biochemical responses were compared in both strains.Eighteen days after PG‐PS injection, rats with normal concentrations of HK showed weight loss and marked increase in hind ankle diameter with severe synovial inflammation and cartilage abnormalities. In contrast, HK‐deficient rats showed no weight loss (P < 0.05), no increase in hind ankle diameter (P < 0.05), and an absence of inflammatory changes (P < 0.05), as measured by the histologic and morphometric Mankin grading system for synovial and cartilage injury.Plasma HK is a key mediator of acute and chronic inflammatory arthritis in genetically susceptible Lewis rats. [ABSTRACT FROM AUTHOR]