A recent Brain, Behavior and Immunity study indicates that psychological stress contributes to the exacerbation of the murine model of colitis by promoting the mobilization and entry of neutrophils in the colon.
This appears to be achieved by the up-regulation of pro-inflammatory cytokine and chemokine production and STAT3 signaling, and involves β1/β2-adrenergic receptors activation.
Inflammatory bowel disease (IBD) involves chronic inflammation of the digestive tract, and mainly includes ulcerative colitis and Crohn’s disease. In the 1950s IBD was classified as a psychosomatic disorder, and more recent evidence implicates psychological stress in the pathogenesis of the chronic inflammation in this condition. The mechanisms that drive stress-induced inflammation in IBD remain, however, poorly understood.
Neutrophils are the most abundant phagocyte and innate immune cells of the human blood. In pathological conditions, their mobilization in the tissues contributes to tissue damage, inflammation, and the release of proinflammatory mediators such as IL-8, TNF-α, IL-6, IL-1β as well as reactive oxygen species. In response to stress, the sympathetic nervous system and the adrenal medulla release neurotransmitters and hormones, such as norepinephrine (noradrenaline) and epinephrine (adrenaline), which influence the activity and function of immune cells through activation of α- and β-adrenergic receptors. This also includes effects on the mobilization and traffic of lymphocytes, granulocytes and neutrophils.
In the Brain, Behavior and Immunity study, Que Deng and colleagues from the Institute of Basic Medical Sciences, Beijing, China found that chronic restraint stress and chronic unpredictable stress worsened dextran sulfate sodium (DSS)-induced colitis in mice. This included high weight loss, intestinal mucosa erosions and ulcerations, and increased epithelial permeability.
The authors report that the experimental stress promoted neutrophils infiltration, overactivation of STAT3 signaling and an increased expression of proinflammatory cytokines, such as IL-1β, IL-6, IL-17A and IL-22. The hyperactivation of the STAT3 inflammatory pathway was linked to an overexpression of pivotal neutrophils and chemokines i.e. CXCL1, CXCL2, CXCL5 and CXCL15.
Of note, the activation of the β-adrenergic receptor pathway aggravated this inflammatory state because the β-adrenergic agonist isoproterenol mimicked the effect of stress on neutrophil functions through the activation of β1/β2-adrenergic receptors. Moreover, the β1/β2-adrenoceptor antagonist propranolol was able to prevent the neutrophil infiltration into the colonic tissue and reduced the tissue damage.
This study suggests that psychological stress can exacerbate the inflammatory process in IBD acting on the sympathetic nervous system and through catecholamine-mediated activation of β1/β2-adrenoceptors is able to increase neutrophil mobilization and infiltration within the colon.
This may reveal a new mechanism of stress-induced inflammation in the gut, and may indicate that beside the classical therapeutic strategies, alternative approaches such as psychological supportand/or manipulation of the β1/β2-adrenoceptor or STAT3 signaling have the potential to reduce the levels of inflammation in IBD.