alexa Emerging Mechanisms of Action and Loss of Response to I
ISSN: 2167-0501

Biochemistry & Pharmacology: Open Access
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Review Article

Emerging Mechanisms of Action and Loss of Response to Infliximab in Ibd: A Broader Picture

Franco Scaldaferri1, Silvia Pecere1*, Daria D’Ambrosio1, Stefano Bibbò1, Valentina Petito1, Loris Riccardo Lopetuso1, Diego Currò2, Marco Pizzoferrato1, Gianluca Ianiro1, Antonio Gasbarrini1# and Giovanni Cammarota1#
1Department of Internal Medicine, Gastroenterology Division, Catholic University of Sacred Hearth, Rome, Italy
2Institute of pharmacology, Catholic University of Sacred Hearth, Rome, Italy
#Equal Contributors
*Corresponding Author : Silvia Pecere
Department of Internal Medicine
Gastroenterology Division
Catholic University of Sacred Hearth, Rome, Italy
Tel: 00393270365655
E-mail: [email protected]
Received: March 15, 2016 Accepted: April 27, 2016 Published: April 30, 2016
Citation: Scaldaferri F, Pecere S, D’Ambrosio D, Bibbò S, Petito P, et al. (2016) Emerging Mechanisms of Action and Loss of Response to Infliximab in Ibd: A Broader Picture. Biochem Pharmacol (Los Angel) 5:206. doi:10.4172/2167-0501.1000206
Copyright: © 2016 Scaldaferri F, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Biologic drugs, as Infliximab (IFX), are widely used in inflammatory bowel disease (IBD). IFX is a chimeric monoclonal immunoglobulin directed against TNF-α and acting in IBD through several mechanisms of action. We divide these mechanisms into central and peripheral. Central mechanisms are considered effective at systemic level, like the reduction of plasmatic pro-inflammatory cytokines (TNF-α, IFN-γ), the promotion of apoptosis of inflammatory cells, the induction of T regulatory cells (FOXP3CD4+) and the modulation of cellular inflammatory pathways. Peripheral mechanisms could be considered acting at mucosal levels like normalization of endothelial functions, blockade of angiogenesis, restoring balance between matrix metalloproteinases (MMPs) and tissue inhibitors of matalloproteases (TIMPs). This classification could serve as solid guide to better categorize mechanisms of lack of response to IFX, which account for up to 30% of patients per year. Central mechanism of loss of response proposed are the formation of antiinfliximab antibodies (ATI), trough serum levels, metabolic factors and pharmacogenomics; peripheral mechanisms of loss of response could be the degradation of IFX by MMPs at mucosal level and the loss of IFX trough inflamed mucosa. In the present review, we analyze mechanisms of action and loss of response to IFX in course of IBD known until today.


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