Role of interleukin‐6 in hypoxic regulation of intestinal iron absorption

Summary The regulation of intestinal iron absorption is not fully understood. Hepcidin, a liver‐produced peptide, has recently been identified as a negative regulator of iron absorption in various conditions associated with altered iron metabolism (e.g. inflammation, anaemia, hypoxia). It is not clear whether these perturbants share a common signalling pathway. In this study, the importance of the cytokine interleukin‐6 (IL‐6) was investigated in the hypoxic mouse model. Hypoxia was associated with increased levels of circulating IL‐6, decreased liver hepcidin mRNA and increased iron absorption (especially MT). A significant positive correlation existed between the total iron uptake and IL‐6 levels in circulation. IL‐6 per se, though inducing hepcidin mRNA, failed to affect basal iron absorption. The adaptive response to absorption following the hypoxic exposure was, however, more prominent if mice had been treated concurrently with IL‐6. This enhancement in absorption occurred even though hepcidin mRNA was not significantly changed. Similar prominent responses were seen with both human and mouse IL‐6. Anti‐IL‐6 antiserum normalised iron absorption in mice exposed to hypoxia, because of a reduction in the MT. These data indicate that IL‐6 can influence iron absorption (especially MT) during the hypoxic exposure, but via a mechanism independent of hepcidin.