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


CONCLUSIONS
Plasma HK is a key mediator of acute and chronic inflammatory arthritis in genetically susceptible Lewis rats.
Sainz
Irma M
IM
Temple University, Philadelphia, PA 19140, USA.
Isordia-Salas
Irma
I
Castaneda
Julian L
JL
Agelan
Alexis
A
Liu
Bo
B
DeLa Cadena
Raul A
RA
Pixley
Robin A
RA
Adam
Albert
A
Sartor
R Balfour
RB
Colman
Robert W
RW
D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D001835:Body Weight; D004338:Drug Combinations; D005528:Foot / Q000473:pathology; D006614:Hindlimb; D007274:Injections, Intraperitoneal; D007596:Joints / Q000473:pathology; D016234:Kallikrein-Kinin System; D019679:Kininogen, High-Molecular-Weight / Q000172:deficiency*; D010457:Peptidoglycan / Q000008:administration & dosage; D011134:Polysaccharides / Q000008:administration & dosage; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew
D004338:Drug Combinations; D019679:Kininogen, High-Molecular-Weight; D010457:Peptidoglycan; D011134:Polysaccharides