Soluble complement receptor one (sCR1) inhibits the development and progression of rat collagen-induced arthritis.
We set out to determine whether inhibition of complement using sCR1 could influence the development and progression of collagen arthritis in the Lewis rat. Collagen arthritis was successfully established in the Lewis rat, using a novel immunization schedule. In separate experiments, cobra venom factor (CVF) and sCR1 were used to achieve systemic complement inhibition. Their respective effects on disease onset and on the progression of established disease compared with saline-treated control animals was explored. Arthritis was assessed by measurement of clinical score, paw diameter and paw volume. Complement inhibition using either CVF or sCR1, prior to the onset of clinical signs of inflammation, delayed the development of disease. CVF was ineffective in the treatment of established disease, whereas sCR1 delayed the progression of disease in affected joints and prevented the recruitment of further joints while the animals were complement-depleted. In the control saline-treated groups the disease continued to progress relentlessly. We conclude that complement activation is important in the initiation and maintenance of inflammation in collagen arthritis. The potent disease-modulating effect of sCR1 provides persuasive evidence that specific complement inhibiting agents may be an effective approach to the treatment of inflammatory joint diseases
Goodfellow
R M
RM
Department of Rheumatology, University of Wales College of Medicine, Cardiff, UK.
Williams
A S
AS
Levin
J L
JL
Williams
B D
BD
Morgan
B P
BP
D000818:Animals; D001168:Arthritis / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control; D003094:Collagen / Q000276:immunology; D003169:Complement Inactivator Proteins / Q000627:therapeutic use; D004195:Disease Models, Animal; D004546:Elapid Venoms / Q000627:therapeutic use; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D017463:Receptors, Complement 3b / Q000627:therapeutic use*; D012995:Solubility; D013997:Time Factors
D003169:Complement Inactivator Proteins; D004546:Elapid Venoms; D017463:Receptors, Complement 3b; C016310:cobra venom factor; D003094:Collagen