title: Fecal lipocalin 2, a sensitive and broadly dynamic non-invasive biomarker for intestinal inflammation.
abstract: Inflammation has classically been defined histopathologically, especially by the presence of immune cell infiltrates. However, more recent studies suggest a role for "low-grade" inflammation in a variety of disorders ranging from metabolic syndrome to cancer, which is defined by modest elevations in pro-inflammatory gene expression. Consequently, there is a need for cost-effective, non-invasive biomarkers that, ideally, would have the sensitivity to detect low-grade inflammation and have a dynamic range broad enough to reflect classic robust intestinal inflammation. Herein, we report that, for assessment of intestinal inflammation, fecal lipocalin 2 (Lcn-2), measured by ELISA, serves this purpose. Specifically, using a well-characterized mouse model of DSS colitis, we observed that fecal Lcn-2 and intestinal expression of pro-inflammatory cytokines (IL-1β, CXCL1, TNFα) are modestly but significantly induced by very low concentrations of DSS (0.25 and 0.5%), and become markedly elevated at higher concentrations of DSS (1.0 and 4.0%). As expected, careful histopathologic analysis noted only modest immune infiltrates at low DSS concentration and robust colitis at higher DSS concentrations. In accordance, increased levels of the neutrophil product myeloperoxidase (MPO) was only detected in mice given 1.0 and 4.0% DSS. In addition, fecal Lcn-2 marks the severity of spontaneous colitis development in IL-10 deficient mice. Unlike histopathology, MPO, and q-RT-PCR, the assay of fecal Lcn-2 requires only a stool sample, permits measurement over time, and can detect inflammation as early as 1 day following DSS administration. Thus, assay of fecal Lcn-2 by ELISA can function as a non-invasive, sensitive, dynamic, stable and cost-effective means to monitor intestinal inflammation in mice.
authors.affiliation: Department of Biology, Center for Inflammation, Immunity and Infection, Georgia State University, Atlanta, Georgia, United States of America.
authors.forename: Benoit
authors.initials: B
authors.lastname: Chassaing
authors.forename: Gayathri
authors.initials: G
authors.lastname: Srinivasan
authors.forename: Maria A
authors.initials: MA
authors.lastname: Delgado
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Young
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Gewirtz
authors.forename: Matam
authors.initials: M
authors.lastname: Vijay-Kumar
mesh_terms: D000209:Acute-Phase Proteins / Q000096:biosynthesis* / Q000502:physiology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D054360:Chemokine CXCL1 / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005243:Feces; D005260:Female; D007249:Inflammation; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000378:metabolism*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000096:biosynthesis* / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000378:metabolism; D015513:Oncogene Proteins / Q000096:biosynthesis* / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D053583:Interleukin-1beta; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D014409:Tumor Necrosis Factor-alpha; C071332:Lcn2 protein, mouse; D016753:Interleukin-10; D009195:Peroxidase