BACKGROUND: In recent studies, sepsis and endotoxemia were associated with increased IL-6 production in mucosa of the jejunum. We tested the hypothesis that endotoxemia in mice stimulates mucosal IL-6 production in other parts of the gastrointestinal tract as well and that the enterocyte is a source of mucosal IL-6. In addition, we examined the effects of TNF alpha and IL-1 beta on mucosal IL-6 production. MATERIALS AND METHODS: Endotoxin (12.5 mg/kg) was injected subcutaneously in mice. Control mice were injected with a corresponding volume of sterile saline. After 4 h, IL-6 levels were determined in mucosa of stomach, jejunum, ileum, and colon and in plasma and liver. In a second series of experiments, immunohistochemistry was performed of jejunal mucosa to determine in which cell type IL-6 was expressed. Finally, 100 micrograms/kg of human recombinant TNF alpha or human recombinant IL-1 beta was injected intraperitoneally in mice and IL-6 levels were determined in plasma and tissues after 4 h. RESULTS: Endotoxemia resulted in increased mucosal IL-6 levels in small and large bowel but in reduced IL-6 levels in gastric mucosa. Immunohistochemistry of jejunal mucosa showed that IL-6 was expressed mainly in the enterocyte and in a few cells of the lamina propria. Treatment of mice with TNF alpha reduced IL-6 levels in gastric mucosa whereas IL-1 beta increased IL-6 levels in mucosa of small intestine. CONCLUSION: Mucosal IL-6 production during endotoxemia is differentially regulated along the gastrointestinal tract. Both TNF alpha and IL-1 beta may be involved in the regulation of gastrointestinal IL-6 production during endotoxemia.
BACKGROUND: In recent studies, sepsis and endotoxemia were associated with increased IL-6 production in mucosa of the jejunum. We tested the hypothesis that endotoxemia in mice stimulates mucosal IL-6 production in other parts of the gastrointestinal tract as well and that the enterocyte is a source of mucosal IL-6. In addition, we examined the effects of TNF alpha and IL-1 beta on mucosal IL-6 production. MATERIALS AND METHODS: Endotoxin (12.5 mg/kg) was injected subcutaneously in mice. Control mice were injected with a corresponding volume of sterile saline. After 4 h, IL-6 levels were determined in mucosa of stomach, jejunum, ileum, and colon and in plasma and liver. In a second series of experiments, immunohistochemistry was performed of jejunal mucosa to determine in which cell type IL-6 was expressed. Finally, 100 micrograms/kg of human recombinant TNF alpha or human recombinant IL-1 beta was injected intraperitoneally in mice and IL-6 levels were determined in plasma and tissues after 4 h. RESULTS:Endotoxemia resulted in increased mucosal IL-6 levels in small and large bowel but in reduced IL-6 levels in gastric mucosa. Immunohistochemistry of jejunal mucosa showed that IL-6 was expressed mainly in the enterocyte and in a few cells of the lamina propria. Treatment of mice with TNF alpha reduced IL-6 levels in gastric mucosa whereas IL-1 beta increased IL-6 levels in mucosa of small intestine. CONCLUSION: Mucosal IL-6 production during endotoxemia is differentially regulated along the gastrointestinal tract. Both TNF alpha and IL-1 beta may be involved in the regulation of gastrointestinal IL-6 production during endotoxemia.
Authors: Dennis I Sonnier; Amy T Makley; Lou Ann W Friend; Stephanie R Bailey; Alex B Lentsch; Timothy A Pritts Journal: J Surg Res Date: 2011-03-31 Impact factor: 2.192
Authors: QingHe Meng; Haroon A Choudry; Wiley W Souba; Anne M Karinch; JingLi Huang; ChengMao Lin; Thomas C Vary; Ming Pan Journal: J Gastrointest Surg Date: 2005-12 Impact factor: 3.267