Nielsen and Ainsworth (Aug. 22 issue)1 state that etanercept is not effective in the treatment of inflammatory bowel disease because it may lack the capacity to induce mucosal T-cell apoptosis in the way that antibody-based tumor necrosis factor (TNF) inhibitors do. Infliximab and adalimumab induce apoptosis of activated monocytes.2 Certolizumab pegol does not induce apoptosis of T cells or monocytes3 but is effective in Crohn's disease. Furthermore, several studies have shown that etanercept, like adalimumab and infliximab, can induce apoptosis.4 These observations indicate that additional modes of action are involved in the efficacy of TNF inhibitors in inflammatory bowel disease. Despite widespread use of these therapies in patients with this disease, their precise mechanism of action remains unclear, although several different mechanisms have been proposed. Recently, a new mechanism of action of infliximab and certolizumab pegol was identified; it involved the modulation of nonapoptotic pathways through down-regulation of proinflammatory growth differentiation factor 1 (GDF-1).5 These effects require further investigation in vivo.