Abstract
Background: We have shown that transgenic (TG) mice overexpressing IL-10 in the intestine have a significant survival advantage over their wildtype (WT) counterparts when challenged with cecal ligation and puncture (CLP). The mechanism underlying this survival advantage is unknown. Objective: To determine mechanisms responsible for the survival advantage conferred by intestine-specific overexpression of IL- 10. Methods: Given the documented role of IL-10 on systemic inflammation, the gut, and the lungs, each was examined in detail in septic TG and WT mice. TG (n=13) and WT (n=14) mice were subjected to CLP with a 1 by 27 injury. The animals were sacrificed 24 hours later and intestines, lungs, serum, and bronchoalveolar lavage (BAL) fluid were collected. The serum and BAL were spun down and assayed for cytokines IL-12, TNFa, IFN, MCP-1, IL-10, and IL-6 using cytometric bead analysis. Intestines and lungs were sectioned and stained by H&E. Intestines were assessed for epithelial apoptosis in 100 intact crypt-villus units while the lungs were assessed qualitatively. A piece of the intestine was also used to evaluate permeability utilizing the everted gut sac model. Results: IL-12 levels were lower (p <.05) in the serum of transgenic mice (5.1 +/− 0.5 vs. 6.7 +/− 0.5) with no significant differences in the other serum or BAL cytokines measured. There was no statistically significant disparity in intestinal apoptosis, and lung histology was unremarkable. Evaluation of clearance in the intestine revealed no significant difference in permeability. Conclusions: Intestinal production of IL-10, an anti-inflammatory cytokine, induces a minor downstream block of systemic IL-12 expression in septic animals but has no effect on other serum or BAL cytokines, gut permeability and apoptosis, and lung histology. The main mechanisms underlying the survival advantage conferred by intestinal overexpression of IL-10 remain to be determined.
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