Although antagonists of this cytokine are highly effective at ameliorating inflammation when given to mice with established colitis, animals with a genetic deficiency of TNF are more susceptible to acute colitis than wildtype animals, with a 60% 7-day mortality compared to 0% in control animals.24 The dichotomous effects of this pivotal cytokine supports the concept of the “phasic” nature of CD pathogenesis and suggests that the same cytokines that have a deleterious effect during chronic inflammation may confer protection in the preceding acute inflammatory response. The gene discussed is TNF; the disease is Cowden disease.