The current study poses an intriguing mechanistic explanation for the deleterious effects of anti-TNF-α treatments on heart failure; while antagonism to the soluble TNF-α would be desirable, since it indeed mediates cardiomyocyte hypertrophy and triggers further expression of the pro-inflammatory cytokines interleukin 1 beta (IL-1β) and interleukin 6 (Il-6), the blockade of the protective membrane-bound form tmTNF-α would disrupt its beneficial effects. The gene discussed is IL1B; the disease is heart failure.