PURPOSE: AI is present in the majority of patients in the ICU. The iron regulatory hormone hepcidin is presumed to be the principal mediator of AI since it is upregulated during inflammation and induces an iron-restricted anemia with preserved iron stores. The purpose of this study is to determine whether hepcidin antagonism is an effective treatment for AI.
METHODS: To model AI, we used two sterile mouse models of chronic peritonitis. We then used knockout mice to test the importance of hepcidin and its regulators in AI.
RESULTS: Both models induced microcytic anemia in wild type mice. Absence of hepcidin protected against AI in the less severe model of peritonitis. Absence of two important regulators of hepcidin, hemojuvelin and transferrin receptor-2 (TfR2), did not protect against AI.
CONCLUSION: Hepcidin, but not the hemojuvelin or TfR2, protects against AI in less severe inflammation. The hepcidin regulators hemojuvelin and TfR2 may not be necessary for the upregulator of hepcidin during inflammation. AI is a complex disorder caused by iron restriction, bone marrow suppression, and decreased erythrocyte lifespan. The relative contributions of these factors will determine the effectiveness of hepcidin blockade.
CLINICAL IMPLICATIONS: Direct antagonism of hepcidin may be an effective treatment for AI in some ICU patients.
DISCLOSURE: Seth Rivera, No Financial Disclosure Information; No Product/Research Disclosure Information