Vice versa, an increased expression of HAMP leads to circulating-iron restriction; this is a major pathophysiological mechanism underlying the anemia of inflammation, wherein pro-inflammatory interleukin-6 raises hepcidin levels through the STAT pathway, or in iron-refractory iron-deficiency anemia (IRIDA), wherein mutations of the hepcidin inhibitor TMPRSS6 up-regulate the BMP-SMAD pathway [25]. This evidence concerns the gene IL6 and IRIDA syndrome.