Adoptive transfer of macrophage from mice with depression-like behavior enhances susceptibility to colitis.
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.
Farncombe Family Digestive Health Research Institute, Division of Gastroenterology, McMaster University, Hamilton, Ontario, Canada.
Jean-Eric
JE
Ghia
Amber J
AJ
Park
Patricia
P
Blennerhassett
Waliul I
WI
Khan
Stephen M
SM
Collins
D019264:Adoptive Transfer; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D015153:Blotting, Western; D002097:C-Reactive Protein / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000209:etiology* / Q000523:psychology*; D003866:Depressive Disorder / Q000150:complications* / Q000276:immunology / Q000523:psychology; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000150:complications / Q000276:immunology / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000502:physiology; D017737:Macrophages, Peritoneal / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010275:Parasympathetic Nervous System / Q000276:immunology; D014628:Vagotomy; D014630:Vagus Nerve / Q000276:immunology
D000928:Antidepressive Agents; D018836:Inflammation Mediators; D016173:Macrophage Colony-Stimulating Factor; D002097:C-Reactive Protein; D016264:Dextran Sulfate