Heightened responses to stressors in patients with inflammatory bowel disease.
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.
Farhadi
Ashkan
A
Department of Internal Medicine, Section of Gastroenterology and Nutrition, Rush University Medical Center, Chicago, Illinois 60612, USA.
Keshavarzian
Ali
A
Van de Kar
Louis D
LD
Jakate
Shriram
S
Domm
Aaron
A
Zhang
Lei
L
Shaikh
Maliha
M
Banan
Ali
A
Fields
Jeremy Z
JZ
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*
D011506:Proteins; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone