title: Inflammatory intestinal damage induced by 5-fluorouracil requires IL-4.
abstract: BACKGROUND
  5-Fluorouracil (5-FU) induces intestinal mucositis, which is characterized by epithelial ulcerations in the mucosa and clinical manifestations, such as pain and dyspeptic symptoms. Cytokines participate in the inflammatory and functional events of intestinal mucositis. IL-4 is an important mediator of intestinal inflammation, with either anti-inflammatory or pro-inflammatory functions, depending on the model of intestinal inflammation. This study aimed to evaluate the role of IL-4 in 5-FU-induced intestinal mucositis.
  
  
  METHODS
  IL-4+/+ or IL-4-/- mice (25-30 g) were intraperitoneally injected with 5-FU (450 mg/Kg) or saline (C). After 3 days, the mice were sacrificed and the duodenum was evaluated for epithelial damage, MPO activity and cytokine concentration.
  
  
  RESULTS
  5-FU induced significant damage in the intestinal epithelium of IL-4+/+ mice (reduction in the villus/crypt ratio: control=3.31±0.21 μm, 5-FU=0.99±0.10 μm). However, the same treatment did not induce significant damage in IL-4-/- mice (5-FU=2.87±0.19 μm) compared to wild-type mice. 5-FU-induced epithelial damage increased the MPO activity (neutrophil number) and the level of pro-inflammatory cytokines (IL-4, TNF-α, IL-1β and CXCL-8) in the duodenum. These results were not observed in IL-4-/- mice treated with 5-FU.
  
  
  CONCLUSIONS
  Our data suggest that IL-4 participates as a pro-inflammatory cytokine in a 5-FU-induced intestinal damage model and suggests that IL-4 antagonists may be novel therapeutics for this condition.
authors.affiliation: Departamento de Morfologia, Universidade Federal do Ceará, Brazil. pedrogsoares@yahoo.com.br
authors.forename: Pedro M G
authors.initials: PM
authors.lastname: Soares
authors.forename: José Maurício S C
authors.initials: JM
authors.lastname: Mota
authors.forename: Emmanuel P
authors.initials: EP
authors.lastname: Souza
authors.forename: Priscilla F C
authors.initials: PF
authors.lastname: Justino
authors.forename: Alvaro X
authors.initials: AX
authors.lastname: Franco
authors.forename: Fernando Q
authors.initials: FQ
authors.lastname: Cunha
authors.forename: Ronaldo A
authors.initials: RA
authors.lastname: Ribeiro
authors.forename: Marcellus H L P
authors.initials: MH
authors.lastname: Souza
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000494:pharmacology; D004386:Duodenum / Q000276:immunology* / Q000293:injuries; D005472:Fluorouracil / Q000009:adverse effects / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics* / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D007422:Intestines / Q000276:immunology / Q000293:injuries; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052016:Mucositis / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000964:Antimetabolites, Antineoplastic; C508606:CXCL8 protein, human; D053583:Interleukin-1beta; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D005472:Fluorouracil