Acceleration of onset of collagen-induced arthritis by intra-articular injection of tumour necrosis factor or transforming growth factor-beta.
We examined whether tumour necrosis factor (TNF) or transforming growth factor-beta 1 (TGF-beta 1) could alter the course of collagen-induced arthritis (CIA). Injection of 100 ng TNF or 500 ng TGF-beta 1 into ankle joints of normal rats induced a very limited inflammatory response, observable only upon histological analysis. However, when injected into ankle joints of rats 9 days after immunization with bovine type II collagen (CII), identical doses of TNF or TGF-beta 1 induced a sustained, clinically obvious inflammation and oedema that began within 8 h on average, as compared to 90 h in CII-immunized control rats given no injections or intra-articular injections of buffer. The incidence of arthritis at 2 weeks post-immunization was 100% for TNF-injected hindpaws, compared with 55% for the control groups, a statistically significant difference. In rats passively immunized with a subarthritic dose of affinity purified antibody to rat-CII, intra-articular injection of 100 ng TNF or 500 ng of TGF-beta 1 also induced intense, though transient arthritis. The rapid proinflammatory effects in CIA described in this study and the synergy demonstrated between anti-CII IgG and either cytokine, suggest that these cytokines can participate locally in the pathogenesis of arthritis.
Cooper
W O
WO
Department of Veterans Affairs Medical Centre, Department of Medicine, Nashville, TN 37212.
Fava
R A
RA
Gates
C A
CA
Cremer
M A
MA
Townes
A S
AS
D000818:Animals; D001168:Arthritis / Q000209:etiology*; D003094:Collagen / Q000276:immunology*; D005260:Female; D007114:Immunization; D009504:Neutrophils / Q000276:immunology; D051381:Rats; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen