title: Heightened responses to stressors in patients with inflammatory bowel disease.
abstract: OBJECTIVE
  Several studies suggest that stressful situations (stressors) worsen the course of inflammatory bowel disease (IBD), but the mechanism is not known. Based on several lines of evidence, we hypothesized that psychosocial stress activates the brain-gut axis (BGA) and mucosal mast cells (MC), and activated MC produce proinflammatory cytokines. To test this hypothesis, we determined whether stressor-induced activation of BGA is exaggerated in IBD patients.
  
  
  METHODS
  Stress was induced in 15 IBD patients who were in remission (inactive IBD) and in seven controls by a widely used stressor, the cold pressor test (CPT), daily for five consecutive days. Induction of stress was confirmed objectively by measurement of stress hormones (serum cortisol and ACTH), and hemodynamic parameters and subjectively by questionnaire. Activation of the BGA by this stressor was assessed by evaluating colonic mucosal MC histology and degranulation, using electron microscopy (EM). The effects of the stressor on the intestinal mucosa were assessed by changes in inflammatory cell histology, epithelial mitochondria (EM), and oxidative tissue injury (assays for protein oxidation).
  
  
  RESULTS
  In both study groups, the stressor resulted in (1) increased levels of stress hormones, (2) the expected changes in hemodynamic parameters, (3) activation and degranulation of MC, (4) mitochondrial damage to epithelial cells, and (5) mucosal protein oxidation. These changes were more marked in IBD patients.
  
  
  CONCLUSIONS
  The heightened response to the stressors and the greater epithelial damage in IBD patients suggests that stress-induced activation of the BGA and of mucosal MC is important in the initiation and/or flare up of IBD.
authors.affiliation: Department of Internal Medicine, Section of Gastroenterology and Nutrition, Rush University Medical Center, Chicago, Illinois 60612, USA.
authors.forename: Ashkan
authors.initials: A
authors.lastname: Farhadi
authors.forename: Ali
authors.initials: A
authors.lastname: Keshavarzian
authors.forename: Louis D
authors.initials: LD
authors.lastname: Van de Kar
authors.forename: Shriram
authors.initials: S
authors.lastname: Jakate
authors.forename: Aaron
authors.initials: A
authors.lastname: Domm
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Maliha
authors.initials: M
authors.lastname: Shaikh
authors.forename: Ali
authors.initials: A
authors.lastname: Banan
authors.forename: Jeremy Z
authors.initials: JZ
authors.lastname: Fields
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D001794:Blood Pressure; D015550:Cell Degranulation; D003080:Cold Temperature; D003106:Colon / Q000473:pathology; D005260:Female; D006339:Heart Rate; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007150:Immunohistochemistry; D015212:Inflammatory Bowel Diseases / Q000473:pathology / Q000503:physiopathology*; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D008875:Middle Aged; D008928:Mitochondria / Q000648:ultrastructure; D018384:Oxidative Stress; D011506:Proteins / Q000378:metabolism; D013312:Stress, Physiological / Q000503:physiopathology*
chemical_list: D011506:Proteins; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone