title: Analysis of IL-22 contribution to hepcidin induction and hypoferremia during the response to LPS in vivo.
abstract: The anaemia of chronic disease (ACD) results from inflammation-mediated up-regulation of the iron regulatory hormone hepcidin, with the consequent sequestration of iron limiting its availability for erythropoiesis. The inflammatory cytokine IL-6, a regulator of hepcidin, has been implicated in this process. Recent in vivo and in vitro studies indicate that IL-22 is also able to stimulate hepcidin expression. We aimed to determine if IL-22 had a role in causing the hypoferremia associated with the inflammatory response. Wild-type and Il22-knockout mice were subjected to an acute inflammatory stimulus via administration of LPS and the response of hepcidin and iron homeostasis was analysed. In the absence of IL-22, there was a response of hepcidin, resulting in a reduction in serum iron levels. However, the hypoferremic response to LPS was slightly blunted in mice lacking IL-22, suggesting that, during LPS-mediated inflammation, IL-22 may play a minor role in mediating the hypoferremic response. These results may have implications for the treatment and management of the ACD.
authors.affiliation: Membrane Transport Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia and School of Medicine, University of Queensland, Brisbane, Queensland 4006, Australia.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Wallace
authors.affiliation: Membrane Transport Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia and School of Medicine, University of Queensland, Brisbane, Queensland 4006, Australia Nathan.Subramaniam@qimrberghofer.edu.au.
authors.forename: V Nathan
authors.initials: VN
authors.lastname: Subramaniam
mesh_terms: D000740:Anemia / Q000139:chemically induced / Q000276:immunology*; D000818:Animals; D004195:Disease Models, Animal; D004920:Erythropoiesis / Q000235:genetics; D064451:Hepcidins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology*; D015850:Interleukin-6 / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D015854:Up-Regulation; D000097043:Interleukin-22
chemical_list: D064451:Hepcidins; D015850:Interleukin-6; D007378:Interleukins; D007501:Iron; D008070:Lipopolysaccharides; D000097043:Interleukin-22
keywords: IL-22; anaemia of chronic disease; hepcidin; inflammation; iron