Psychological stress reactivates dextran sulfate sodium-induced chronic  colitis in mice.
Inflammatory bowel disease (IBD) is a chronic condition with alternating active and quiescent phases of inflammation. Stress has been suggested as a factor triggering a relapse of IBD. We investigated the role of repetitive psychological stress [water avoidance stress (WAS)] in reactivating colonic inflammation in a murine model of dextran sulfate sodium (DSS)-induced chronic colitis. Colitis was induced in C57BL/6 female mice by exposure to 3% DSS (5 days). During chronic inflammation(day 34), mice underwent repetitive WAS (1 h/day/7 days) and were given a sub-threshold concentration of DSS (1%, 5 days)or normal water to drink. At euthanasia (day 40), inflammatory parameters were assessed (colon inflammatory score, levels of inflammatory markers and histology). Mice with chronic colitis exposed to WAS had higher macroscopic and microscopic colonic inflammatory scores and levels of inflammatory markers (mainly IL-1beta, IL12p40 and CCL5) than non-stressed mice. Inflammatory responses were further enhanced by the presence of a sub-threshold concentration of DSS (1%). In mice without chronic inflammation, neither WAS nor 1% DSS, individually or in combination, elicited any inflammation. Hence stress, per se, reactivates a quiescent chronic inflammation, but does not initiate inflammation in healthy mice. Stress should be regarded as an environmental factor triggering IBD relapses in humans.
Melgar
S
S
Department of Integrative Pharmacology, AstraZeneca R&D Mölndal, Mölndal, Sweden.
Engström
K
K
Jägervall
A
A
Martinez
V
V
D000311:Adrenal Glands / Q000033:anatomy & histology; D000818:Animals; D001362:Avoidance Learning; D018946:Chemokine CCL5 / Q000097:blood; D054360:Chemokine CXCL1 / Q000097:blood; D003092:Colitis / Q000139:chemically induced* / Q000473:pathology; D003345:Corticosterone / Q000097:blood; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D005260:Female; D006242:Haptoglobins / Q000378:metabolism; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000209:etiology; D018664:Interleukin-12 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009929:Organ Size; D012008:Recurrence; D013154:Spleen / Q000033:anatomy & histology; D013315:Stress, Psychological / Q000150:complications*; D013950:Thymus Gland / Q000033:anatomy & histology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C503460:Ccl5 protein, mouse; D018946:Chemokine CCL5; D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D006242:Haptoglobins; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D016264:Dextran Sulfate; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D003345:Corticosterone