Brief Article
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World J Gastrointest Pathophysiol. Dec 15, 2012; 3(6): 102-108
Published online Dec 15, 2012. doi: 10.4291/wjgp.v3.i6.102
Inverse relationship of interleukin-6 and mast cells in children with inflammatory and non-inflammatory abdominal pain phenotypes
Wendy A Henderson, Ravi Shankar, Tara J Taylor, Arseima Y Del Valle-Pinero, David E Kleiner, Kevin H Kim, Nader N Youssef
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
David E Kleiner, Department of Health and Human Services, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, United States
Kevin H Kim, School of Psychology in Education, University of Pittsburgh, Pittsburgh, PA 15260, United States
Nader N Youssef, Digestive Healthcare Center, Hillsborough, NJ 08844, United States
Author contributions: Henderson WA and Youssef NN designed the study; all of the authors were involved in writing and editing the manuscript; Shankar R and Taylor TJ performed the majority of the experiments; Kim KH provided statistical analysis support.
Supported by The Intramural Research Program of the National Institute of Nursing Research (to Henderson WA, 1ZIANR000018-01-04, 2009), National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, United States; SAIC-Fredrick contractor to the National Cancer Institute (NCI Contract NO. HHSN261200800001E)
Correspondence to: Dr. Wendy A Henderson, Biobehavioral Branch, Intramural Research Program, NINR, NIH, DHHS, NIH Clinical Research Center, Building 10, 2-1339, Bethesda, MD 20892, United States. hendersw@mail.nih.gov
Telephone: +1-301-4519534 Fax: +1-301-4801413
Received: December 16, 2011
Revised: November 16, 2012
Accepted: December 6, 2012
Published online: December 15, 2012
Abstract

AIM: 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.

CONCLUSION: 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.

Keywords: Histopathology, Colon, Interleukin-6, Mast cells, Substance P