Interleukin 13 and serotonin: linking the immune and endocrine systems in murine models of intestinal inflammation

PLoS One. 2013 Aug 28;8(8):e72774. doi: 10.1371/journal.pone.0072774. eCollection 2013.


Objective: Infiltration of activated immune cells and increased cytokine production define the immunophenotype of gastrointestinal (GI) inflammation. In addition, intestinal inflammation is accompanied by alteration in the numbers of serotonin (5-hydroxytryptamine; 5-HT) synthesizing enterochromaffin (EC) cells and in 5-HT amount. It has been established that EC cells express interleukin (IL)-13 receptor, additionally IL-13 has been implicated in the pathogenesis of ulcerative colitis. In this study, we investigated the role of IL-13 mediated 5-HT signaling in pathogenesis of colitis.

Methodology: Colitis was induced in IL-13 deficient (IL-13-/-) and wild-type (WT) mice with dextran sulfate sodium (DSS) and dinitrobenzene sulfonic acid (DNBS), as well as in IL-13-/- mice given recombinant mouse IL-13 (rmIL-13) and 5-hydroxytryptamine (5-HTP), the direct precursor of 5-HT.

Principal findings and conclusion: Elevated colonic IL-13 levels were observed in WT mice receiving DSS in comparison to control. IL-13-/- mice administered DSS exhibited significantly reduced severity of colitis compared to WT mice as reflected by macroscopic and histological damage assessments. Following DSS administration, significantly lower pro-inflammatory cytokine production and fewer infiltrating macrophages were observed in IL-13-/- mice compared to WT. The reduced severity of colitis observed in IL-13-/- mice was also accompanied by down-regulation of EC cell numbers and colonic 5-HT content. In addition, increasing colonic 5-HT content by administration of rmIL-13 or 5-HTP exacerbated severity of DSS colitis in IL-13-/- mice. IL-13-/- mice also exhibited reduced severity of DNBS-induced colitis. These results demonstrate that IL-13 plays a critical role in the pathogenesis of experimental colitis and 5-HT is an important mediator of IL-13 driven intestinal inflammation. This study revealed important information on immune-endocrine axis in gut in relation to inflammation which may ultimately lead to better strategy in managing various intestinal inflammatory conditions including inflammatory bowel disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzenesulfonates / toxicity
  • Colitis / chemically induced
  • Colitis / genetics
  • Colitis / immunology
  • Colitis / metabolism*
  • Colitis / pathology
  • Dextran Sulfate / toxicity
  • Disease Models, Animal
  • Endocrine System / immunology
  • Endocrine System / metabolism*
  • Endocrine System / pathology
  • Interleukin-13 / genetics
  • Interleukin-13 / immunology
  • Interleukin-13 / metabolism*
  • Interleukin-13 / pharmacology
  • Macrophages, Peritoneal / immunology
  • Macrophages, Peritoneal / metabolism*
  • Macrophages, Peritoneal / pathology
  • Mice
  • Mice, Knockout
  • Serotonin / genetics
  • Serotonin / immunology
  • Serotonin / metabolism
  • Serotonin / pharmacology


  • Benzenesulfonates
  • Interleukin-13
  • dinitrobenzenesulfonic acid
  • Serotonin
  • Dextran Sulfate