Several studies have clearly indicated that autophagy can suppress inflammatory reactions [42,45-47]. For instance, loss of autophagy proteins, e.g. Atg16L1, potentiates endotoxin-induced IL-1β production [48]. Moreover, genetic studies have revealed that two autophagy genes, Atg16L1 and IRGM are associated with the pathogenesis of Crohn×s disease, an inflammatory bowel disease [39]. It is known that autophagy regulates the inflammatory reaction, e.g. in adipocytes [49] and keratinocytes [50]. Meng and Cai [51] demonstrated that defective autophagy in hypothalamus induced inflammation and subsequently led to obesity and insulin resistance when mice were fed a high-fat diet. Interestingly, these workers observed that the effects of reduced autophagy were reversed by the inhibition of inhibitory-κB kinase β (IKKβ) indicating that inflammation was induced by NF-κB signaling. On the other hand, potentiation of autophagy, e.g. by inhibitors of mammalian target of rapamycin (mTOR) and activators of AMP-activated protein kinase (AMPK), can reduce inflammation and tissue pathology in several diseases [39,45,52] (see also below). Shi et al. [53] demonstrated in human macrophages that increasing the autophagy by starvation and rapamycin treatment reduced CASP-1 activity and secretion of
