Iron-related immune cell function in sepsis

Abstract

Sepsis is characterized by a dysregulated immune response to infection, causing damage to tissues and organs. As part of the inflammatory response, iron catalyzes the generation of reactive oxygen species (ROS). In the present study, we sought to evaluate the anti-inflammatory effects of a novel iron chelator, DIBI, in vitro and in two murine models of sepsis in vivo. In vitro, we found that DIBI reduced ROS production by innate immune cells. In vivo immune cell activation was evaluated in the intestinal microcirculation using intravital microscopy. In both sepsis models, anti-inflammatory actions were observed upon administration of DIBI, whereby DIBI reduced sepsis-induced leukocyte adhesion and preserved capillary perfusion in the intestinal microvasculature. Therefore, our data presents a promising role for iron chelation as a therapeutic option for sepsis, in which DIBI reduces ROS generation by binding iron.