Effect of Infliximab and Adalimumab on Experimental Colitis Following Orally Supplemented Iron

J Invest Surg. 2017 Feb;30(1):6-12. doi: 10.1080/08941939.2016.1215574. Epub 2016 Aug 18.

Abstract

Background: Orally administered iron can induce colonic inflammation in healthy animals and aggravate experimental colitis.

Aim: To investigate the influence of the biologic agents infliximab and adalimumab on the severity of TNBS colitis following orally supplemented iron.

Materials-methods: 204 Wistar rats were allocated into 14 groups. Colitis was induced by TNBS. Iron was administered via a mouth catheter at a dose of 0.027, 0.3, and 3%/kg diet per day, respectively. Infliximab was subcutaneously administered on the 2nd and 6th day in a dose of 5 mg/kgBW, while adalimumab was administered on the 2nd day in a dose of 2 mg/kgBW. On the 8th day, all animals were euthanatized. Activity of colitis and extent of tissue damage were assessed histologically. Tissue Tumor Necrosis Factor-α (t-TNF-α) and malondialdehyde (t-MDA) were estimated.

Results: In normal rats both agents significantly worsen the degree of inflammation induced by moderate or high iron supplementation despite the disappearance of t-TNF-α, and reduction of t-MDA. In the groups of TNBS colitis and moderate or high iron administration, both agents again significantly worsen the degree of inflammation despite the significant reduction in the t-TNF-α and t-MDA.

Conclusion: Adalimumab and infliximab do not ameliorate the inflammation in TNBS-induced colitis aggravated by orally administered iron. These findings might be clinically relevant in patients with active IBD under concurrent treatment with biologic agents and per oral iron.

Keywords: Crohn's disease; adalimumab; anemia; biologic agents; experimental colitis; inflammatory bowel disease; infliximab; iron; ulcerative colitis.

MeSH terms

  • Adalimumab / therapeutic use*
  • Anemia / drug therapy
  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Colon / metabolism
  • Disease Models, Animal
  • Humans
  • Inflammatory Bowel Diseases / chemically induced
  • Inflammatory Bowel Diseases / drug therapy*
  • Infliximab / therapeutic use*
  • Intestinal Mucosa / drug effects
  • Iron / administration & dosage
  • Iron / adverse effects*
  • Iron / therapeutic use
  • Male
  • Malondialdehyde / metabolism
  • Rats
  • Rats, Wistar
  • Trinitrobenzenesulfonic Acid / toxicity
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Tumor Necrosis Factor-alpha
  • Malondialdehyde
  • Trinitrobenzenesulfonic Acid
  • Infliximab
  • Iron
  • Adalimumab