A monoclonal antibody to high-molecular weight kininogen is therapeutic in a rodent model of reactive arthritis.
We reported that high-molecular weight kininogen is proangiogenic by releasing bradykinin and that a monoclonal antibody to high-molecular weight kininogen, C11C1, blocked its binding to endothelial cells. We now test if this antibody can prevent arthritis and systemic inflammation in a Lewis rat model. We studied 32 animals for 16 days. Group I (negative control) received saline intraperitoneally. Group II (disease-treated) received peptidoglycan-polysaccharide simultaneously with C11C1. Group III (disease-untreated) received peptidoglycan-polysaccharide simultaneously with isotype-matched mouse IgG. Group IV (disease-free-treated) and group V (disease-free isotype-treated) received saline and C11C1 or mouse IgG. Analysis of joint diameter changes showed a decrease in the C11C1 disease-treated group compared to the disease-untreated group. The hind paw inflammatory score showed a decrease in the intensity and extent of inflammation between the disease-untreated and the C11C1 disease-treated group. Prekallikrein, high-molecular weight kininogen, factor XI, and factor XII were decreased in the disease-untreated group compared to the C11C1 disease-treated group. T-kininogen was increased in the disease-untreated group when compared with the C11C1 disease-treated group. Disease-free groups IV and V did not show any sign of inflammation at any time. This study shows that monoclonal antibody C11C1 attenuates plasma kallikrein-kinin system activation, local and systemic inflammation, indicating therapeutic potential in reactive arthritis.
The Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
Ricardo G
RG
Espinola
Audrey
A
Uknis
Irma M
IM
Sainz
Irma
I
Isordia-Salas
Robin
R
Pixley
Raul
R
DeLa Cadena
Walter
W
Long
Alexis
A
Agelan
John
J
Gaughan
Albert
A
Adam
Robert W
RW
Colman
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D016918:Arthritis, Reactive / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D004195:Disease Models, Animal; D005172:Factor XI / Q000378:metabolism; D005174:Factor XII / Q000378:metabolism; D005260:Female; D006801:Humans; D019679:Kininogen, High-Molecular-Weight / Q000276:immunology*; D018919:Neovascularization, Physiologic / Q000276:immunology; D010457:Peptidoglycan; D051381:Rats; D011917:Rats, Inbred Lew
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D019679:Kininogen, High-Molecular-Weight; D010457:Peptidoglycan; D005174:Factor XII; D005172:Factor XI