Chronic IL‐22Fc administration induces liver hepcidin expression and relative iron deficiency anemia.

Abstract

Interleukin‐22 (IL‐22), a member of the IL‐10 cytokine family, is produced by activated TH17 and NK cells and binds to a specific heterodimeric receptor expressed on epithelium of the skin, respiratory and digestive tracts and hepatocytes. In vitro, IL‐22 stimulates hepatoma cell lines to express α1‐antichymotrypsin, haptoglobin, serum amyloid A, and in vivo administration stimulates LPS binding protein expression by the liver. Treatment of C57BL/6 mice with IL‐22Fc for either 9 days (200 μg I.P. SID) or 4 weeks (150 μg I.P., 3 times per week) induced hypochromic anemia associated with a decreased serum iron concentration, suggesting relative iron deficiency. Given that IL‐22 is also known as “hepatocyte stimulating factor” and iron balance is partially controlled by hepatic expression of the protein hepcidin, we measured serum hepcidin levels by mass spectrometer analysis. Animals treated with IL‐22 had elevated serum hepcidin levels as compared to controls. Previously reported to be elevated in chronically inflamed tissues, IL‐22 may participate in the anemia of chronic inflammatory disease through hepcidin‐induced alterations of iron metabolism.