Characterisation of Acute Murine Dextran Sodium Sulphate Colitis: Cytokine Profile and Dose Dependency

Abstract

Background/Aims: In our experience with the acute murine dextran sodium sulphate (DSS) model of experimental colitis, we noted both interstrain and interanimal variations in daily water consumption. One might critically question whether observed differences in injuries are just a dose dependency phenomenon reflecting variations in DSS intake. To clarify this important topic, we performed a dose and concentration dependency study of DSS in Balb/c mice. We also determined Th1 and Th2 cytokine levels to compare the cytokine profile to that from inflammatory bowel disease (IBD). Methods: In four groups (14 animals each group) different concentrations of DSS (0, 2.5, 5 and 7.5%) were given for 7 days ad libitum. Mucosal injury of the entire colon was histologically assessed and graded. Cytokine levels were determined by competitive quantitative RT-PCR. Results: A linear increase in the crypt damage score was noted with increasing concentrations (0, 4.9 ± 0.7, 11.9 ± 0.5 and 18.9 ± 1.3, respectively), but the total dose of DSS intake did not correlate with mucosal damage. Progressive upregulation in the transcripts for Th1 cytokines (IL-12, IFN-γ, IL-1, TNF-α) was observed with increasing dosage of DSS. Interestingly, an increase in IL-10, but not IL-4 mRNA transcripts was also noted. Discussion: Acute DSS-induced mucosal injury is dependent on the administered DSS water concentration but not on the consumed DSS dose. The cytokine profile is a classic Th1 response and is similar to that of various inflammatory conditions in the colon. Conclusions: Minor variations in fluid consumption do not affect the severity of DSS-induced injury in mice. The acute murine DSS colitis model is useful for studying the pathophysiological aspects of colonic inflammatory diseases as IBD and for evaluating new potential therapeutic agents

Blockade of CXCL10 protects mice from acute colitis and enhances crypt cell survival

“…5C). Although DSS-induced chronic colitis has been reported to be a Th1-dominant disease [6,31], we could not confirm significant Th1 cell infiltration in situ [32] by day 5. Since acute DSS-induced colitis could be induced even in SCID mice, which lack T cells [22], it is likely that DSS directly injures the epithelium.…”

β-Caryophyllene Inhibits Dextran Sulfate Sodium-Induced Colitis in Mice through CB2 Receptor Activation and PPARγ Pathway

“…61,62 The T H 1 cytokines encompass the cytokine profile of acute murine DSSinduced colitis (INF-␥, TNF-␣, and IL-1␤). 63 In T H 1 cells, the recruitment of phospho-CREB is significantly higher than in T H 2 cells. 64 In the present study, we demonstrated that BCP treatment decreased DSS-induced CREB activation, which may be linked to decreased T H 1 cytokines, such as INF-␥, and the enhancement of T H 2 cytokines, namely IL-4.…”

Inhibitory Effect of Recombinant IL-25 on the Development of Dextran Sulfate Sodium-Induced Experimental Colitis in Mice

“…DSS-induced experimental colitis model is still regarded as a reliable model for the IBD cellular and molecular studies (4). It has been reported that the Th1 cytokine response and histological changes in acute DSSinduced colitis model resemble those observed in human IBDs (5).…”