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

Autor: Irma Isordia-Salas, Robert W. Colman, Robin A. Pixley, Raul A. DeLa Cadena, Julian L. Castaneda, Albert Adam, Irma M. Sainz, Alexis Agelan, Bo Liu, R. Balfour Sartor
Rok vydání: 2005
Předmět:
Zdroj: Arthritis & Rheumatism. 52:2549-2552
ISSN: 1529-0131
0004-3591
DOI: 10.1002/art.21202
Popis: 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.
Databáze: OpenAIRE