title: Locally injected Infliximab ameliorates murine DSS colitis: differences in serum and intestinal levels of drug between healthy and colitic mice.
abstract: 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-α, 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-α. Human IgG were used as controls. DSS model of colitis on C57BL/6 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-α and murine-TNF-α. 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, Gastroenterology Division, IBD Unit, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Loris Riccardo
authors.initials: LR
authors.lastname: Lopetuso
authors.forename: Valentina
authors.initials: V
authors.lastname: Petito
authors.forename: Valerio
authors.initials: V
authors.lastname: Cufino
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Arena
authors.forename: Egidio
authors.initials: E
authors.lastname: Stigliano
authors.forename: Viviana
authors.initials: V
authors.lastname: Gerardi
authors.forename: Eleonora
authors.initials: E
authors.lastname: Gaetani
authors.forename: Andrea
authors.initials: A
authors.lastname: Poscia
authors.forename: Arianna
authors.initials: A
authors.lastname: Amato
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cammarota
authors.forename: Alfredo
authors.initials: A
authors.lastname: Papa
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sgambato
authors.forename: Antonio
authors.initials: A
authors.lastname: Gasbarrini
authors.forename: Franco
authors.initials: F
authors.lastname: Scaldaferri
mesh_terms: D061605:Administration, Intravenous; D000285:Administration, Rectal; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000032:analysis / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000032:analysis / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D016264:Dextran Sulfate; D004733:Enema; D005243:Feces / Q000737:chemistry*; D000069285:Infliximab; D007413:Intestinal Mucosa / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D016264:Dextran Sulfate; D000069285:Infliximab
keywords: Faeces; Inflammatory bowel disease; Infliximab; Intestinal mucosa; Murine DSS colitis; Pharmacokinetic; Serum levels