Role of IL-10 for induction of anemia during inflammation.
Anemia is frequently observed in patients suffering from chronic inflammatory disorders. Recent in vitro data suggest that Th2 cytokines, such as IL-10, could be involved in its pathogenesis. We analyzed 1) changes in hemoglobin values in 329 patients with chronic active Crohn's disease receiving the anti-inflammatory cytokine IL-10 as part of a randomized, double-blind, placebo-controlled study, 2) serum iron parameters in a subgroup of these patients (n = 54), and 3) the in vitro effects of IL-10 on ferritin transcription and translation in human monocytic cells (THP-1) by means of Northern blot and immunoprecipitation after metabolic labeling. Patients receiving higher doses of IL-10 developed anemia and presented with a dose-dependent increase of ferritin and soluble transferrin receptor levels, an indicator of iron restriction to erythroid progenitor cells. According to our in vitro data, hyperferritinemia may result from direct stimulation of ferritin translation by IL-10 in activated monocytic cells, most likely by cytokine-mediated reduction of the binding affinity of translational repressors, iron-regulatory proteins, to the 5'-untranslated region of ferritin mRNA. In patients, all observed changes were most pronounced at the end of therapy (day +29), and thereafter hemoglobin levels and serum iron parameters returned to baseline levels within 4 wk of follow-up. Our data demonstrate that IL-10 causes anemia in patients with inflammatory bowel disease which may be referred to the induction of imbalances in iron homeostasis by the cytokine, leading to hyperferritinemia and limited iron availability to erythroid progenitor cells, a condition typically seen in the anemia of chronic inflammation.
Tilg
Herbert
H
Division of Gastroenterology and Hepatology, Department of Medicine, University Hospital Innsbruck, Innsbruck, Austria.
Ulmer
Hanno
H
Kaser
Arthur
A
Weiss
Günter
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000740:Anemia / Q000097:blood / Q000209:etiology*; D003424:Crohn Disease / Q000097:blood / Q000150:complications* / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015672:Erythroid Precursor Cells / Q000378:metabolism; D005293:Ferritins / Q000378:metabolism; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000008:administration & dosage / Q000009:adverse effects* / Q000502:physiology; D007501:Iron / Q000097:blood / Q000378:metabolism; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects
D006454:Hemoglobins; D011994:Recombinant Proteins; D016753:Interleukin-10; D005293:Ferritins; D007501:Iron