ENDOTOXEMIA AND IL-1-BETA STIMULATE MUCOSAL IL-6 PRODUCTION IN DIFFERENT PARTS OF THE GASTROINTESTINAL-TRACT

Background In recent studies, sepsis and endotoxemia were associated w ith 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 ent erocyte is a source of mucosal IL-6. In addition, we examined the effe cts of TNF-alpha and IL-1 beta on mucosal IL-6 production. Materials a nd Methods. Endotoxin (12.5 mg/kg) was injected subcutaneously in mice . Control mice were injected with a corresponding volume of sterile sa line. After 4 h, IL-6 levels were determined in mucosa of stomach, jej unum, ileum, and colon and in plasma and liver. In a second series of experiments, immunohistochemistry was performed of jejunal mucosa to d etermine in which cell type IL-6 was expressed. Finally, 100 mu g/kg o f human recombinant TNF alpha or human recombinant IL-1 beta was injec ted intraperitoneally in mice and IL-6 levels were determined in plasm a and tissues after 4 h. Results. Endotoxemia resulted in increased mu cosal 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 i n gastric mucosa whereas IL-1 beta increased IL-6 levels in mucosa of small intestine. Conclusion. Mucosal IL-6 production during endotoxemi a is differentially regulated along the gastrointestinal tract. Both T NF alpha and IL-1 beta may be involved in the regulation of gastrointe stinal IL-6 production during endotoxemia. (C) 1998 Academic Press.