Reduced intestinal inflammation induced by dextran sodium sulfate in interleukin-6-deficient mice

Abstract

Interleukin-6 (IL-6) is a multifunctional cytokine secreted by various cells, and is involved in the acute phase response and the immune response through T and B cell activation. To further define the role of IL-6 in intestinal inflammation, we studied the effects of dextran sulfate sodium (DSS) administration in mice with targeted deletions of the IL-6 gene. Acute colitis was induced in female IL-6-/- and IL-6+/+ mice by giving 4.5% DSS orally in drinking water for 8 days. The colonic mucosal injury and inflammation was evaluated based on survival rate, body-weight changes, total colon length and histological findings. Colonic mRNA expression for tumor necrosis factor (TNF)-alpha, IL-6, IL-10 and inducible nitric oxide synthase (iNOS) was measured by RT-PCR. Colonic IL-6 mRNA levels of wild-type mice continued to increase throughout the study period. At each assessment, colonic injury was significantly attenuated in DSS-treated IL-6-/- mice compared with DSS-treated IL-6+/+ mice. Histological study also showed a reduced infiltration of inflammatory cells, especially neutrophils, and mucosal cell disruption in DSS-treated IL-6-/- mice compared with DSS-treated IL-6+/+ mice. In the colons of DSS-treated IL-6-/- mice, the expression of both TNF-alpha mRNA and iNOS mRNA was reduced on day 5. In contrast, IL-10 mRNA expression was enhanced compared with DSS-treated IL-6+/+ mice. In conclusion, DSS-induced inflammation appears to be significantly inhibited in IL-6-/- mice compared to wild-type mice. These data suggest that persistent and marked blockade of IL-6 bioactivity provides some beneficial effects on intestinal inflammation.