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The gut as a source of inflammatory cytokines after stimulation with endotoxin
C K Ogle1, X Guo, P O Hasselgren
1Department of Surgery, College of Medicine, University of Cincinnati, Ohio, USA.
Objective:
To find out if endotoxin (LPS) can mediate the production of inflammatory cytokines by enterocytes.
Design:
Laboratory experiment.
Setting:
Teaching hospital and burns unit, USA.
Material:
Caco-2 cells (HTB38, human adenocarcinoma, and colon).
Main Outcome Measures:
Concentrations of tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and prostaglandin E2 (PGE2) in cell culture supernatants.
Results:
LPS significantly increased the production of TNF from 8.9 to 26.4 units/ml in 24 h and this increase persisted at a lower level for 4 days with an increase from 2.3 to 9 units/ml at a cell concentration of 2 x 10(5) cells/ml. There was no increase in TNF production when the cells were cultured at 5 x 10(5) cells ml with LPS. At a concentration of 2 x 10(5) cells/ml, the cells produced small amounts of IL-6 in 24 h or 4 day cultures with or without LPS. At a concentration of 5 x 10(5) cells/ml, LPS significantly increased IL-6 production in 24 h from 142 to 433 units/ml and from 106 to 250 units/ml in 4 days. The amount of IL-6 produced by LPS-stimulated cells was greater at 1 day than at 4 days. There was no significant difference in PGE2 production by the cells under any of the incubation conditions.
Conclusion:
Enterocytes can produce TNF and IL-6, and endotoxin can increase the production of these cytokines by enterocytes. The gut therefore has the potential to become an important source of inflammatory cytokines.