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

Inflamm Bowel Dis. 2011 Jul;17(7):1474-89. doi: 10.1002/ibd.21531. Epub 2011 Jan 18.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antidepressive Agents / therapeutic use
  • Blotting, Western
  • C-Reactive Protein / metabolism
  • Colitis, Ulcerative / etiology*
  • Colitis, Ulcerative / psychology*
  • Depressive Disorder / complications*
  • Depressive Disorder / immunology
  • Depressive Disorder / psychology
  • Dextran Sulfate / toxicity
  • Disease Models, Animal
  • Disease Susceptibility
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Immunoenzyme Techniques
  • Inflammation / complications
  • Inflammation / immunology
  • Inflammation / pathology
  • Inflammation Mediators / metabolism
  • Macrophage Colony-Stimulating Factor / physiology
  • Macrophages, Peritoneal / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Parasympathetic Nervous System / immunology
  • Vagotomy
  • Vagus Nerve / immunology


  • Antidepressive Agents
  • Inflammation Mediators
  • Macrophage Colony-Stimulating Factor
  • C-Reactive Protein
  • Dextran Sulfate