Animal models of chemically induced intestinal inflammation: predictivity and ethical issues.

The debate about the ethical and scientific issues regarding the use of animals in research is mainly focused on these questions: a) whether preclinical studies in animals are still ethically acceptable; b) whether it is possible to establish more soundly their predictivity; c) what measures should be taken to reduce the clinical attrition often due to biased preclinical assessment of potential efficacy of new drugs. This review aims at a critical revision of animal models of chemically induced intestinal inflammation in drug development. These models, notwithstanding differences among species, still represent a major source of information about biological systems and can have undisputable translational value, provided that appropriate measures are taken to ensure that experiments are both scientifically and ethically justified. These measures include: a) more stringent application to preclinical experiments of standards used in clinical studies (such as sample size, randomization, inclusion/exclusion criteria, blinding); b) selection of the animal model after careful pathophysiological scrutiny bearing in mind inherent limitations of each model (e.g. acute self-limiting vs chronic disease, animal species, role of the intestinal immune system and microbiome); and c) experimental design duly considering the specific pharmacological profile of each agent to be screened (such as bioavailability, route of administration, full consideration of the pharmacological spectrum). In this perspective, the new European legislation is an opportunity to fully apply these standards so that in vivo animal models can provide an invaluable mean to study complex physiological and biochemical interactions, which cannot be completely simulated in silico and/or in vitro.