Fecal Lipocalin 2, a Sensitive and Broadly Dynamic Non-Invasive Biomarker for Intestinal Inflammation

Benoit Chassaing, Gayathri Srinivasan, Maria A. Delgado, Andrew N. Young, Andrew T. Gewirtz, Matam Vijay Kumar

Research output: Contribution to journalArticle

146 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere44328
JournalPloS one
Volume7
Issue number9
DOIs
StatePublished - Sep 5 2012

Fingerprint

Lipocalins
Biomarkers
biomarkers
inflammation
Inflammation
colitis
Colitis
Peroxidase
myeloperoxidase
Assays
mice
Enzyme-Linked Immunosorbent Assay
enzyme-linked immunosorbent assay
Interleukin-1
Gene expression
Interleukin-10
Costs and Cost Analysis
Costs
metabolic syndrome
interleukin-1

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Chassaing, B., Srinivasan, G., Delgado, M. A., Young, A. N., Gewirtz, A. T., & Kumar, M. V. (2012). Fecal Lipocalin 2, a Sensitive and Broadly Dynamic Non-Invasive Biomarker for Intestinal Inflammation. PloS one, 7(9), [e44328]. https://doi.org/10.1371/journal.pone.0044328
Chassaing, Benoit ; Srinivasan, Gayathri ; Delgado, Maria A. ; Young, Andrew N. ; Gewirtz, Andrew T. ; Kumar, Matam Vijay. / Fecal Lipocalin 2, a Sensitive and Broadly Dynamic Non-Invasive Biomarker for Intestinal Inflammation. In: PloS one. 2012 ; Vol. 7, No. 9.
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Chassaing, B, Srinivasan, G, Delgado, MA, Young, AN, Gewirtz, AT & Kumar, MV 2012, 'Fecal Lipocalin 2, a Sensitive and Broadly Dynamic Non-Invasive Biomarker for Intestinal Inflammation', PloS one, vol. 7, no. 9, e44328. https://doi.org/10.1371/journal.pone.0044328

Fecal Lipocalin 2, a Sensitive and Broadly Dynamic Non-Invasive Biomarker for Intestinal Inflammation. / Chassaing, Benoit; Srinivasan, Gayathri; Delgado, Maria A.; Young, Andrew N.; Gewirtz, Andrew T.; Kumar, Matam Vijay.

In: PloS one, Vol. 7, No. 9, e44328, 05.09.2012.

Research output: Contribution to journalArticle

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