title: Fecal Lipocalin-2 as a Sensitive and Noninvasive Biomarker in the TNBS Crohn's Inflammatory Bowel Disease Model.
abstract: Colitis induced by 2,4,6-Trinitrobenzenesulfonic acid (TNBS) has been used as a model for Crohn's disease (CD) of inflammatory bowel disease (IBD). Lipocalin-2 (Lcn-2) is an emerging and clinically relevant biomarker of IBD. We investigated the performance of serum and fecal Lcn-2 in the TNBS model of colitis. Female, 7-week-old, BALB/c mice were administered intrarectally phosphate-buffered saline/water or 30% ethanol (vehicle control groups) for 5 days or TNBS for 5 days followed by a 28-day recovery phase. Serum and fecal levels of Lcn-2 were quantified, and effects on body weight, clinical scores, colon weight and length, gross pathology, and histopathology were investigated. Increased serum Lcn-2 levels correlated only with marked to severe inflammation. A clear differentiation in Lcn-2 fecal levels between TNBS-treated and vehicle-treated control mice was most noticeable on days 2 and 3. There was a strong correlation between body weight change, histopathologic scores of inflammation, and/or fecal Lcn-2 levels on days 2 and 5. Both serum and fecal Lcn-2 levels declined over time as the colonic mucosa recovered. Fecal Lcn-2 was found to be a more sensitive biomarker (vs. serum Lcn-2) and was able to discriminate mild, moderate, and severe colonic inflammation.
authors: 1 Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors: Heidi
authors: H
authors: Hsieh
authors: 2 Pfizer Worldwide Research and Development, Andover, Massachusetts, USA.
authors: Jeffrey
authors: J
authors: Morin
authors: 2 Pfizer Worldwide Research and Development, Andover, Massachusetts, USA.
authors: Cyndi
authors: C
authors: Filliettaz
authors: 2 Pfizer Worldwide Research and Development, Andover, Massachusetts, USA.
authors: Rao
authors: R
authors: Varada
authors: 2 Pfizer Worldwide Research and Development, Andover, Massachusetts, USA.
authors: Shelby
authors: S
authors: LaBarre
authors: 2 Pfizer Worldwide Research and Development, Andover, Massachusetts, USA.
authors: Zaher
authors: Z
authors: Radi
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D003106:Colon / Q000473:pathology; D003424:Crohn Disease / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D004195:Disease Models, Animal; D005243:Feces / Q000737:chemistry*; D005260:Female; D000071068:Lipocalin-2 / Q000032:analysis* / Q000097:blood; D008807:Mice, Inbred BALB C; D012107:Research Design; D012680:Sensitivity and Specificity; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D000071068:Lipocalin-2; D014302:Trinitrobenzenesulfonic Acid
keywords: Crohn’s disease; IBD; TNBS; biomarker; lipocalin-2