Locally injected Infliximab ameliorates murine DSS colitis: Differences in serum and intestinal levels of drug between healthy and colitic mice

Background: Infliximab is effective in human and murine IBD, but its pharmacodynamic is still poorly known. The aim of this study was to assess the affinity of infliximab to murine TNF-alpha, its role in murine colitis when administered intra-rectally and its levels in the blood, gut mucosa and stool of healthy and sick mice. Methods: An ELISA kit was built in order to assess the affinity of infliximab to human or murine-TNF-alpha. Human IgG were used as controls. DSS model of colitis on C57BL16 mice was used to assess clinical efficacy of infliximab administered intravenously or by enema. Stool, serum and colon samples were collected to assess infliximab levels and histology for Rachmilewitz score. Results: Infliximab showed a good affinity both for human-TNF-alpha and murine-TNF-alpha. In DSS colitic mice infliximab ameliorated the severity of colitis, regardless of the administration route. In comparison with colitic mice, healthy mice displayed higher serum and mucosal infliximab levels, while detectable levels of infliximab were found in faeces, particularly in colitic mice. Conclusion: Our data support murine models to study infliximab pharmacokinetics and dynamics. Measurable levels of infliximab can be found at different concentrations in blood, intestinal mucosa and stool from healthy and sick mice, thus infliximab pharmacokinetics could have a major impact in human IBD. (C) 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.