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Adoptive transfer of macrophage from mice with depression-like behavior enhances susceptibility to colitis

Authors

  • Jean-Eric Ghia PhD,

    1. Farncombe Family Digestive Health Research Institute, Division of Gastroenterology, McMaster University, Hamilton, Ontario, Canada
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  • Amber J. Park MSc,

    1. Farncombe Family Digestive Health Research Institute, Division of Gastroenterology, McMaster University, Hamilton, Ontario, Canada
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  • Patricia Blennerhassett MSc,

    1. Farncombe Family Digestive Health Research Institute, Division of Gastroenterology, McMaster University, Hamilton, Ontario, Canada
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  • Waliul I. Khan PhD,

    1. Farncombe Family Digestive Health Research Institute, Division of Gastroenterology, McMaster University, Hamilton, Ontario, Canada
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  • Stephen M. Collins MD

    Corresponding author
    1. Farncombe Family Digestive Health Research Institute, Division of Gastroenterology, McMaster University, Hamilton, Ontario, Canada
    • Associate Dean, Research, Faculty of Health Sciences, McMaster University Medical Center, Room 2E16, 1200 Main St. West, Hamilton, Ontario L8N 3Z5, Canada
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Abstract

Background:

Depression is common in patients with inflammatory bowel disease (IBD) but the pathway is not well understood. We examined whether the locus of susceptibility to colitis in mice with depression-like behavior (DLB) resides with the macrophage and implicates the vagus nerve.

Methods:

Chronic colitis mimicking ulcerative colitis (UC) was induced by dextran sulfate sodium administered to C57BL/6-mice. Depression was induced by intracerebroventricular infusion of reserpine in healthy or vagotomized mice treated with antidepressant desmethylimipramine (DMI). Colitis was assessed macroscopically, histologically, and by C-reactive protein measurement in serum and by cytokines in colonic samples. Cytokine release was measured on macrophages isolated from these models. Naive macrophage colony-stimulating factor-deficient mice (op/op) were injected with peritoneal macrophages obtained from the different groups and acute colitis was induced.

Results:

Vagotomy reactivated inflammation in mice with chronic colitis. DLB reactivated colitis and this was prevented by DMI only in mice with intact vagi. Macrophages isolated from vagotomized or DLB-mice showed a selective increase of proinflammatory cytokine release and this was not seen in macrophages isolated from DLB-DMI-treated mice; moreover, vagotomy abolished this beneficial effect. In op/op, adoptive transfer of macrophages from non-DLB mice significantly increased the inflammatory markers. These parameters were significantly increased when transferred with macrophages isolated from DLB or VXP mice. Op/op mice that received macrophages from DLB-DMI-treated mice showed a significant decrease of all parameters and vagotomy abolished this effect.

Conclusions:

These data identify the critical role of macrophage in linking depression and susceptibility to intestinal inflammation via the vagus nerve. The results provide a basis for developing new approaches to the management of UC patients with coexisting depression by rebalancing cytokine production by the cell.(Inflamm Bowel Dis 2011;)

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