To the Editor: In their review article on hypoxia and inflammation, Eltzschig and Carmeliet (Feb. 17 issue)1 were thorough in promoting the role of hypoxia-inducible transcription factor (HIF) and related mechanisms to regain homeostasis in hypoxic tissue environments. Although very exacting in its discussion, the review unfortunately failed to include other, equally important mechanisms that lead to inflammation from hypoxic–ischemic reperfusion injury. I am referring in part to the importance of the inflammasome, and in particular to the NLRP3 inflammasome that responds to danger-associated molecular patterns (e.g., urates, free ATP) resulting from nucleoprotein catabolism induced by such injury. Such stimulation leads to secretion of proinflammatory cytokines, in particular interleukin-1β,2 resulting in neutrophilic inflammation. The NLRP3 inflammasome mechanism was first discovered in autosomal autoinflammatory syndromes, namely cryopyrin-associated periodic syndromes, and these disorders have responded beautifully to interleukin-1–targeted therapies. Now there is current interest among several pharmaceutical companies to test similar therapies in inflammatory disorders caused by hypoxic–ischemic reperfusion injury.2-4