Response to Fionula Brennan's Commentary "A follow-up to 'Anti-cytokine therapy in chronic destructive arthritis' by Wim B van den Berg"

In recent years, the effectiveness of anti-TNF therapy in treating rheumatoid arthritis (RA) has become apparent. While trials of IL-1 receptor antagonist in RA have been encouraging, it clearly is more difficult to target two molecules (IL-1 alpha and beta) than one (TNF-alpha). In his review article, Professor Wim van den Berg argues that both TNF-alpha and IL-1 must be blocked in RA and that although TNF is clearly a potent inflammatory molecule, the dominant cytokine in the subsequent degradation of the joint tissue is IL-1. This commentary discusses his hypothesis in light of animal studies and the limitations of the conclusions that can be drawn from them. More broadly, it discusses the biology of TNF-alpha and IL-1 and suggests explanations of why TNF-alpha is a pivotal cytokine in this disease.