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

Authors


Abstract

Objective

To compare inflammatory peripheral arthritis in wild-type and high molecular weight kininogen (HK)–deficient rats, both on the genetically susceptible Lewis background.

Methods

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.

Results

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.

Conclusion

Plasma HK is a key mediator of acute and chronic inflammatory arthritis in genetically susceptible Lewis rats.

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