Chronic psychological stress in rats induces intestinal sensitization to luminal antigens.
There is increasing evidence that stress plays a role in the pathophysiology of chronic intestinal disorders, but the mechanisms remain unclear. Previous studies in rats have revealed that stress decreases gut barrier function and allows excessive uptake of luminal material. Here, we investigated whether chronic psychological stress acts to induce sensitization of intestinal tissues to oral antigens. Rats were subjected to 1 hour per day of water avoidance stress or sham stress daily for 10 days, and horseradish peroxidase (HRP) was delivered by gavage on day 5. Studies to determine sensitization were conducted on day 20. All stressed rats developed HRP-specific IgE antibodies, antigen-induced intestinal secretion, and increased numbers of inflammatory cells in gut mucosa. Luminal HRP was absorbed more readily by enterocytes of stressed animals. In addition, stressed rats had increased expression of interleukin-4 and decreased expression of interferon-gamma in gut mucosa, a cytokine profile that is typical of allergic conditions. Treatment of stressed rats with an antagonist to corticotropin-releasing hormone (previously shown to inhibit stress-enhanced gut permeability) eliminated the manifestations of intestinal hypersensitivity. Our results indicate that the presence of oral antigen during chronic psychological stress alters the immune response (to sensitization rather than oral tolerance) and causes subsequent antigen-induced gut pathophysiology.
Yang
Ping-Chang
PC
Department of Pathology and Molecular Medicine, Intestinal Disease Research Program, McMaster University, Hamilton, Ontario, Canada.
Jury
Jennifer
J
Söderholm
Johan D
JD
Sherman
Philip M
PM
McKay
Derek M
DM
Perdue
Mary H
MH
D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000276:immunology; D005512:Food Hypersensitivity / Q000523:psychology*; D006735:Horseradish Peroxidase / Q000378:metabolism; D007073:Immunoglobulin E / Q000097:blood; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000276:immunology* / Q000648:ultrastructure; D008297:Male; D008407:Mast Cells / Q000276:immunology; D046529:Microscopy, Electron, Transmission; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013315:Stress, Psychological / Q000276:immunology* / Q000503:physiopathology*
D016207:Cytokines; D007073:Immunoglobulin E; D003346:Corticotropin-Releasing Hormone; D006735:Horseradish Peroxidase