Aggravation of DSS-induced colitis after chronic subordinate colony (CSC) housing is partially mediated by adrenal mechanisms

Figures & data

Table I.  Effects of a chronic psycho-social stressor (CSC) on body weight and anxiety-related behaviour on the elevated plus-maze.

		Controls	CSC
Body weight gain [g]		2.4 ± 0.1 (n = 37)	1.7 ± 0.2 ** (n = 39)
Elevated plus-maze(EPM)	% time OA	43.2 ± 4.5 (n = 37)	11.9 ± 1.9 *** (n = 39)
	% entries OA	45.7 ± 3.2 (n = 37)	22.0 ± 1.9 *** (n = 39)
	CA entries	10.7 ± 0.9 (n = 37)	10.4 ± 0.7 (n = 39)

CSC mice gained significantly less body weight during 19 days of CSC exposure. Increased anxiety of CSC mice is reflected by a reduced percentage of time spent on the open arms (% time OA) and reduced percentage of entries into the open arms (% entries OA) during 5 min of testing on the elevated plus-maze. The number of entries into closed arms (CA) reflects the motor activity. Mice were exposed to the CSC stress procedure for 19 days, or were kept individually (control) and were tested on the plus-maze on day 20. Numbers in parentheses indicate number of mice per group. Data represent means ± SEM; ** p < 0.01; *** p < 0.001 vs. unstressed controls.

Figure 1 Effects of prior exposure to CSC on body weight changes from day 1 to 2 [control/DSS; CSC/DSS], day 1 to 4 [control/DSS; CSC/DSS], and day 1 to 8 [control/noDSS; CSC/noDSS; control/DSS; CSC/DSS] of DSS treatment. CSC exposure prior to DSS treatment had no effect on body weight changes from day 1 to 2 and day 1 to 4 of DSS administration. Enhanced body weight loss in CSC mice was found from day 1 to 8 of DSS treatment. Numbers in parenthesis indicate number of mice per group. Data represent mean ± SEM; *** p < 0.001 vs. respective controls; ### p < 0.001 vs. respective group without DSS.

Figure 2 Effects of prior exposure to CSC on the length (A) and the histological damage score (B) of the colon estimated on day 2, day 4, and day 8 of DSS treatment. CSC exposure prior to DSS treatment further reduced colon length on day 8 of DSS treatment. The DSS-induced increase in the histological damage score was more pronounced in CSC mice on day and 8 of DSS treatment. (C) and (D) show two representative colonic haematoxylin and eosin-stained sections [a: Lamina mucosae; b: Lamina muscularis mucosae; c: Lamina submucosae; d: Lamina muscularis (circular muscle); e: Lamina muscularis (longitudinal muscle)] from: (C) non-stressed control mice receiving tap water without DSS for 8 days, with normal colon histology, and (D) non-stressed controls treated with DSS for 8 days, showing crypt loss in large areas; thickening of the mucosa with abundant oedema; infiltration reaching the lamina submucosa. Numbers in parenthesis indicate number of mice per group. Data represent group mean+/ − SEM * p < 0.05 vs. respective controls; ### p < 0.001 vs. respective group without DSS.

Figure 3 Effects of prior exposure to CSC on the secretion of pro-inflammatory [TNF-α (A), IFN-γ (B), IL-6 (C)], and anti-inflammatory [IL-10 (D)] cytokines by mesenteric lymph node cells on day 2, day 4, and day 8 of DSS treatment. CSC exposure prior to DSS treatment increased secretion of all cytokines on day 2 and 4 of DSS administration. On day 8 after CSC exposure cytokine secretion was also increased in CSC mice given tap water only. Numbers in parenthesis indicate number of mice per group. Data represent mean +SEM * p < 0.05; ** p < 0.01; *** p < 0.001 vs. respective controls; ## p < 0.01; ### p < 0.001 vs. respective group without DSS.

Figure 4 Effects of prior exposure to CSC on plasma corticosterone concentrations on day 2, day 4, and day 8 of DSS treatment. Corticosterone concentrations of controls and CSC mice were increased on day 8 of DSS treatment, with the effect being more greater in CSC mice. Numbers in parenthesis indicate number of mice per group. Data represent mean +SEM * p < 0.05 vs. respective controls; ## p < 0.01; ### p < 0.001 vs. respective group without DSS.

Figure 5 Effects of adrenalectomy (ADX) and CSC on the severity of acute colitis on day 8 of DSS treatment (SHAM/control: n = 8; SHAM/CSC: n = 7; ADX/control: n = 8; /ADX/CSC n = 6). ADX one week before exposure to 19 days of CSC reduced the severity of the DSS-induced colitis compared with SHAM mice as indicated by a diminished body weight loss (A), less inflammatory reduction of colonic length (B), a trend towards a lower histological damage score (C), and a reduced secretion of TNF-α (D), IFN-γ (E), IL-6 (F), and IL-10 (E) from mesenteric lymph node cells compared to CSC mice of the SHAM group. Data represent mean ± SEM; * p < 0.05; ** p < 0.01; *** p < 0.001 vs. respective controls; # p < 0.05; ## p < 0.01; ### p < 0.001 vs. respective SHAM group.