title: Inverse relationship of interleukin-6 and mast cells in children with inflammatory and non-inflammatory abdominal pain phenotypes.
abstract: OBJECTIVE
  To investigate interleukin-6 (IL-6), mast cells, enterochromaffin cells, 5-hydroxytryptamine, and substance P in the gastrointestinal mucosa of children with abdominal pain.
  
  
  METHODS
  Formalin-fixed paraffin-embedded gastrointestinal biopsy blocks from patients (n = 48) with non-inflammatory bowel disease (irritable bowel syndrome and functional abdominal pain) and inflammatory bowel disease were sectioned and stained for IL-6, mast cells, enterochromaffin cells, 5-hydroxytryptamine, and substance P. All children had chronic abdominal pain as part of their presenting symptoms. Biopsy phenotype was confirmed by a pathologist, blinded to patient information. Descriptive statistics, chi-square, and independent sample t tests were used to compare differences between the inflammatory and non-inflammatory groups.
  
  
  RESULTS
  The cohort (n = 48), mean age 11.9 years (SD = 2.9), 54.2% females, 90% Caucasian, was comprised of a non-inflammatory (n = 26) and an inflammatory (n = 22) phenotype. There was a significant negative correlation between substance P expression and mast cell count (P = 0.05, r = -0.373). Substance P was found to be expressed more often in female patient biopsies and more intensely in the upper gastrointestinal mucosa as compared to the lower mucosa. There were significantly increased gastrointestinal mucosal immunoreactivity to IL-6 (P = 0.004) in the inflammatory phenotype compared to non-inflammatory. Additionally, we found significantly increased mast cells (P = 0.049) in the mucosa of the non-inflammatory phenotype compared to the inflammatory group. This difference was particularly noted in the lower colon biopsies.
  
  
  CONCLUSIONS
  The findings of this study yield preliminary evidence in identifying biomarkers of undiagnosed abdominal pain in children and may suggest candidate genes for future evaluation.
authors.affiliation: Wendy A Henderson, Ravi Shankar, Tara J Taylor, Arseima Y Del Valle-Pinero, Department of Health and Human Services, Intramural Research Program, National Institutes of Health, Bethesda, MD 20892, United States.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Henderson
authors.forename: Ravi
authors.initials: R
authors.lastname: Shankar
authors.forename: Tara J
authors.initials: TJ
authors.lastname: Taylor
authors.forename: Arseima Y
authors.initials: AY
authors.lastname: Del Valle-Pinero
authors.forename: David E
authors.initials: DE
authors.lastname: Kleiner
authors.forename: Kevin H
authors.initials: KH
authors.lastname: Kim
authors.forename: Nader N
authors.initials: NN
authors.lastname: Youssef
keywords: Colon; Histopathology; Interleukin-6; Mast cells; Substance P