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

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 2^nd and 6^th day in a dose of 5 mg/kgBW, while adalimumab was administered on the 2^nd day in a dose of 2 mg/kgBW. On the 8^th 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::

• experimental colitis
• ulcerative colitis
• Crohn's disease
• inflammatory bowel disease
• iron
• anemia
• infliximab
• adalimumab
• biologic agents

ACKNOWLEDGMENTS

The authors wish to thank Dr. Aikaterini Cherakaki (Biologist, MSc) for her substantial help on t-TNF-α levels measurements. The technical assistance of the staff of the Experimental-Research Center ELPEN (A. Zacharioudaki DVM, M. Karamperi, E. Karampela, MSc, K. Tsarea, A. Karaiskos, N. Psychalakis, Evripides, and Stergios Gerakis) is gratefully acknowledged. This work was financially supported by the Hellenic Society of Gastroenterology, and the Experimental-Research Center, ELPEN Pharma, Athens, Greece.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.