THE GUT AS A SOURCE OF INFLAMMATORY CYTOKINES AFTER STIMULATION WITH ENDOTOXIN

Objective: To find out if endotoxin (LPS) can mediate the production o f inflammatory cytokines by enterocytes. Design: Laboratory experiment . Setting: Teaching hospital and burns unit, USA. Material: Caco-2 cel ls (HTB38, human adenocarcinoma, and colon). Main outcome measures: Co ncentrations of tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and prostaglandin E(2) (PGE(2)) in cell culture supernatants. Results: LPS significantly increased the production of TNF from 8.9 t o 26.4 units/ml in 24 h and this increase persisted at a lower level f or 4 days with an increase from 2.3 to 9 units/ml at a cell concentrat ion of 2 x 10(5) cells/ml. There was no increase in TNF production whe n the cells were cultured at 5 x 10(5) cells/ml with LPS. At a concent ration 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 PGE(2) producti on by the cells under any of the incubation conditions. Conclusion: En terocytes can produce TNF and IL-6, and endotoxin can increase the pro duction of these cytokines by enterocytes. The gut therefore has the p otential to become an important source of inflammatory cytokines.