Biphasic alterations in gastrointestinal transit following endotoxaemia in mice

Lipopolysaccharide (LPS)-induced alterations of gastrointestinal transit were studied in mice using activated charcoal. LPS (10 mg kg-1) induced biphasic alterations of intestinal transit. Increase (acceleration phase) and delay (lag phase) in gastrointestinal transit were observed at 90 and 480 min after LPS injection, respectively. LPS administration induced significant increases in tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and nitrate levels in blood serum with maximal levels observed at 1.5, 4, and 8 h after LPS administration, respectively. The effects of recombinant human lzactoferrin (rhLF) on LPS- induced alteration of gastrointestinal transit, and production of TNF-alpha, IL-1beta and nitrate were also studied. Animals were pretreated with rhLF 24 hours before intraperitoneal administration of LPS. RhLF significantly increased gastrointestinal transit during the lag phase. In addition, rhLF decreased the level of TNF-alpha in endotoxaemic animals. The levels of IL-1beta and nitrate were not significantly changed by rhLF. In conclusion, the effect of LPS on gastrointestinal transit is biphasic and the mechanism controlling the second phase most likely depends on TNF-alpha production, while the first phase most likely does not depend on TNF-alpha. On the other hand, it may be regulated by IL-1beta and nitric oxide production.