Iron supplementation affects the production of pro-inflammatory cytokines in IL-10 deficient mice.
BACKGROUND
Iron supplements may increase disease activity in inflammatory bowel disease through the production of the hydroxyl radical because of its catalytic activity in the Fenton reaction. The purpose of this study was to assess the effect of dietary and locally administered iron in the IL-10 knock-out (-/-) mouse, a model of chronic inflammatory bowel disease.


METHODS
IL10-/- and wild-type mice received a standard or a high-iron diet (35 mg kg(-1) ferrosulphate vs. 500 mg kg(-1) ferrosulphate) after weaning. After 4 weeks the mice were sacrificed. Furthermore, a group of adult IL-10 knock-out mice was given three iron-containing enema's (0.2 mL of 1 mM ferrous-ammonium sulphate) or phosphate buffered saline. These mice were sacrificed after 1 week. Production of pro-inflammatory cytokines by colon tissue cultures, haematological parameters and histology was determined to assess inflammatory activity.


RESULTS
Oral as well as rectal administration of iron resulted in increased pro-inflammatory cytokine production in IL-10-/- mice. Neutrophil counts in IL10-/- on a high iron diet increased as well. No enhanced colonic inflammation was noted on histology after iron supplementation.


CONCLUSIONS
We conclude that dietary or topical administered iron increases pro-inflammatory cytokine production in the colon of IL10-/- mice. No significant increase of histological intestinal inflammation was observed.
Oldenburg
B
B
University Medical Centre Utrecht, The Netherlands. boldenbu@digd.azu.nl
van Berge Henegouwen
G P
GP
Rennick
D
D
Van Asbeck
B S
BS
Koningsberger
J C
JC
D000818:Animals; D003106:Colon / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D004733:Enema; D005296:Ferrous Compounds / Q000494:pharmacology; D006454:Hemoglobins; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology*; D007375:Interleukin-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D019266:Iron, Dietary / Q000494:pharmacology*; D007958:Leukocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000166:cytology; D009924:Organ Culture Techniques; D010976:Platelet Count; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D005296:Ferrous Compounds; D006454:Hemoglobins; D007375:Interleukin-1; D019266:Iron, Dietary; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C020748:ferrous sulfate