Gastroenterology

Gastroenterology

Volume 131, Issue 2, August 2006, Pages 410-419
Gastroenterology

Clinical–alimentary tract
The Effect of Acute Psychologic Stress on Systemic and Rectal Mucosal Measures of Inflammation in Ulcerative Colitis

https://doi.org/10.1053/j.gastro.2006.05.017Get rights and content

Background & Aims: Recent studies suggest that life events and chronic stress increase the risk of relapse in inflammatory bowel disease. Our aim was to study the effects of acute psychologic stress on systemic and rectal mucosal inflammatory responses in patients with inactive ulcerative colitis (UC). Methods: Twenty-five patients with inactive UC and 11 healthy volunteers (HV) underwent an experimental stress test. Ten patients with UC and 11 HV underwent a control procedure. Before and after each procedure, systemic inflammatory response was assessed by serum interleukin (IL)-6 and IL-13 concentrations, tumor necrosis factor (TNF)-α and IL-6 production by lipopolysaccharide (LPS)-stimulated whole blood, leukocyte count, natural killer (NK) cell numbers, platelet activation, and platelet-leukocyte aggregate (PLA) formation. In patients with UC, rectal mucosal inflammation was assessed by TNF-α, IL-13, histamine and substance P release, reactive oxygen metabolite (ROM) production, mucosal blood flow (RMBF) and histology. Results: Stress increased pulse (P < .0001) and systolic BP (P < .0001). In UC, stress increased LPS-stimulated TNF-α and IL-6 production by 54% (P = .004) and 11% (P = .04), respectively, leukocyte count by 16% (P = .01), NK cell count by 18% (P = .0008), platelet activation by 65% (P < .0001), PLA formation by 25% (P = .004), mucosal TNF-α release by 102% (P = .03), and ROM production by 475% (P = .001) and reduced rectal mucosal blood flow by 22% (P = .05). The control protocol did not change any of the variables measured. There were no differences between the responses of the patients with UC and HV. Conclusions: Acute psychologic stress induces systemic and mucosal proinflammatory responses, which could contribute to exacerbations of UC in ordinary life.

Section snippets

Patients and Controls

Twenty-five patients with quiescent UC (13 males; median age, 44 years [range, 28–64]; 32% distal, 20% left-sided, 48% total UC; 76% on 5-ASA, 12% on thiopurines, 4% on methotrexate, none on steroids; median disease duration 10 years [range, 3–31]) and 11 healthy volunteers (HV) (4 males; median age, 27 years [range, 23–56]) underwent the stress protocol. Ten patients with quiescent UC (3 males; median age, 52 years [range, 23–65]; 40% distal, 30% left-sided, 30% total UC; 90% on 5-ASA, 10% on

Autonomic Response to Stress Protocol

The mean of the 3 pulse rate readings measured during the stress protocol was increased compared with pretest values by 7 bpm (median) in patients with quiescent UC (P < .0001) and by 11 bpm in HV (P = .02). Thirty minutes after the end of the stress protocol, the mean pulse rate had returned to baseline in both groups (Table 1).

Mean systolic blood pressure increased during the stress protocol by a median of 12 mm Hg in patients with UC (P < .0001) and 9 mm Hg in HV (P = .03). In patients with

Discussion

In this study, experimental stress caused increases in a range of inflammatory variables, each of which could contribute to stress-induced relapses in UC.

References (48)

  • A. Steptoe et al.

    The influence of psychological stress and socioeconomic status on platelet activation in men

    Atherosclerosis

    (2003)
  • J.D. Soderholm et al.

    Chronic stress induces mast cell-dependent bacterial adherence and initiates mucosal inflammation in rat intestine

    Gastroenterology

    (2002)
  • T.C. Theoharides et al.

    Mast cells as targets of corticotropin-releasing factor and related peptides

    Trends Pharmacol Sci

    (2004)
  • D.R. Ellard et al.

    The effect of a short-term mental stressor on neutrophil activation

    Int J Psychophysiol

    (2001)
  • R.H. Straub et al.

    Association of autonomic nervous hyperreflexia and systemic inflammation in patients with Crohn’s disease and ulcerative colitis

    J Neuroimmunol

    (1997)
  • R.H. Straub et al.

    Uncoupling of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis in inflammatory bowel disease?

    J Neuroimmunol

    (2002)
  • A.M. Milde et al.

    The effects of postnatal maternal separation on stress responsivity and experimentally induced colitis in adult rats

    Physiol Behav

    (2004)
  • G.L. Engel

    Psychological factors in ulcerative colitis in man and gibbon

    Gastroenterology

    (1969)
  • J.E. Mawdsley et al.

    Psychological stress in IBDnew insights into pathogenic and therapeutic implications

    Gut

    (2005)
  • M. Gue et al.

    Stress-induced enhancement of colitis in ratsCRF and arginine vasopressin are not involved

    Am J Physiol

    (1997)
  • B.S. Qiu et al.

    The role of CD4+ lymphocytes in the susceptibility of mice to stress-induced reactivation of experimental colitis

    Nat Med

    (1999)
  • A. Farhadi et al.

    Heightened responses to stressors in patients with inflammatory bowel disease

    Am J Gastroenterol

    (2005)
  • M. Raithel et al.

    Effect of substance P on histamine secretion from gut mucosa in inflammatory bowel disease

    Scand J Gastroenterol

    (1999)
  • A.L. Marsland et al.

    Stability of individual differences in cellular immune responses to acute psychological stress

    Psychosom Med

    (1995)
  • Cited by (109)

    View all citing articles on Scopus

    Supported by the Broad Medical Research Foundation (BMRF).

    View full text