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 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.


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.


CONCLUSIONS
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.
Department of Surgery, University of Cincinnati, Ohio, USA.
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Q
Wang
J J
JJ
Wang
S
S
Boyce
J E
JE
Fischer
P O
PO
Hasselgren
D000818:Animals; D003106:Colon / Q000276:immunology / Q000378:metabolism; D019446:Endotoxemia / Q000276:immunology*; D004731:Endotoxins / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D007082:Ileum / Q000276:immunology / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000032:analysis / Q000096:biosynthesis* / Q000097:blood; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism*; D007583:Jejunum / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D013270:Stomach / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D004731:Endotoxins; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha