Evaluation of TNF-alpha and IL-1 blockade in collagen-induced arthritis and comparison with combined anti-TNF-alpha/anti-CD4 therapy

We have evaluated the effects of anti-TNF-alpha, anti-IL-1, and combined an ti-TNF-alpha /anti-CD4 therapy in collagen-induced arthritis. Blockade of T NF-alpha or IL-1 before disease onset delayed, but did not prevent, the ind uction of arthritis. When treatment was initiated after onset of arthritis, anti-TNF-alpha, anti-IL-1 beta, and anti-IL-1R (which blocks IL-1 alpha an d IL-1 beta) were all found to be effective in reducing the severity of art hritis, with anti-IL-1R and anti-IL-1 beta showing greater efficacy than an ti-TNF-alpha, Anti-IL-1 beta was equally as effective as anti-IL-1R, indica ting that IL-1 beta plays a more prominent role than IL-1 alpha in collagen -induced arthritis. An additive effect was observed between anti-TNF-alpha and anti-IL-1R in the prevention of joint erosion and in normalization of t he levels of serum amyloid P. Combined anti-TNF-alpha /anti-CD4 therapy als o caused normalization of serum amyloid P levels. The therapeutic effect of anti-TNF-cu plus anti-CD4 was comparable to that of anti-TNF-alpha plus an ti-IL-1R, suggesting that combined anti-TNF-alpha /anti-CD4 therapy prevent s both TNF-alpha- and IL-1-mediated pathology. Anti-TNF-alpha treatment red uced IL-1 beta expression in the joint and, conversely, anti-IL-1 beta trea tment reduced TNF-alpha expression, Combined anti-TNF-alpha /anti-CD4 treat ment almost completely blocked the expression of IL-1 beta, thereby confirm ing the ability of this form of combination therapy to prevent IL-1 beta -m ediated pathology.