TNF is a central actor during inflammation and a well-recognized drug target for inflammatory diseases. We found that the mouse strain SPRET/Ei， known for extreme and dominant resistance against TNF-induced shock， displays weak expression of TNF receptor 1 protein (TNFR1) but normal mRNA expression， a trait genetically linked to the major TNFR1 coding gene Tnfrsf1a and to a locus harbouring the predicted TNFR1-regulating miR-511. This miRNA is a genuine TNFR1 regulator in cells. In mice， overexpression of miR-511 down-regulates TNFR1 and protects against TNF， while anti-miR-511 up-regulates TNFR1 and sensitizes for TNF， breaking the resistance of SPRET/Ei. We found that miR-511 inhibits endotoxemia and experimental hepatitis and that this miR is strongly induced by glucocorticoids and is a true TNFR1 modulator and thus an anti-inflammatory miR. Since minimal reductions of TNFR1 have considerable effects on TNF sensitivity， we believe that at least part of the anti-inflammatory effects of glucocorti-coids are mediated by induction of this miR， resulting in reduced TNFR1 expression.