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and IL-1 Blockade in Collagen-Induced Arthritis and Comparison with Combined Anti-TNF-/Anti-CD4 Therapy1
Kennedy Institute of Rheumatology Division, Imperial College School of Medicine, London, United Kingdom
We have evaluated the effects of anti-TNF-
, anti-IL-1,
and combined anti-TNF-/anti-CD4 therapy in collagen-induced
arthritis. Blockade of TNF- or IL-1 before disease onset delayed,
but did not prevent, the induction of arthritis. When treatment was
initiated after onset of arthritis, anti-TNF-, anti-IL-1ß,
and anti-IL-1R (which blocks IL-1 and IL-1ß) were all found to
be effective in reducing the severity of arthritis, with anti-IL-1R
and anti-IL-1ß showing greater efficacy than anti-TNF-.
Anti-IL-1ß was equally as effective as anti-IL-1R, indicating
that IL-1ß plays a more prominent role than IL-1 in
collagen-induced arthritis. An additive effect was observed between
anti-TNF- and anti-IL-1R in the prevention of joint erosion
and in normalization of the levels of serum amyloid P. Combined
anti-TNF-/anti-CD4 therapy also caused normalization of
serum amyloid P levels. The therapeutic effect of anti-TNF- plus
anti-CD4 was comparable to that of anti-TNF- plus
anti-IL-1R, suggesting that combined anti-TNF-/anti-CD4
therapy prevents both TNF-- and IL-1-mediated pathology.
Anti-TNF- treatment reduced IL-1ß expression in the joint and,
conversely, anti-IL-1ß treatment reduced TNF- expression.
Combined anti-TNF-/anti-CD4 treatment almost completely
blocked the expression of IL-1ß, thereby confirming the ability of
this form of combination therapy to prevent IL-1ß-mediated
pathology.
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