Vol. 276, Issue 3, G576-G582, March 1999
Experimental enteropathy in athymic and euthymic rats:
synergistic role of lipopolysaccharide and indomethacin
Hideki
Koga1,
Kunihiko
Aoyagi1,
Takayuki
Matsumoto1,
Mitsuo
Iida2, and
Masatoshi
Fujishima1
1 Second Department of Internal
Medicine, Faculty of Medicine, Kyushu University, Fukuoka 812-8582;
and 2 Division of
Gastroenterology, Department of Medicine, Kawasaki Medical School,
Kurashiki, Okayama 701-0192, Japan
The aim of this
study was to investigate the immunologic and microbiological bases of
indomethacin enteropathy. Athymic nude and euthymic specific
pathogen-free (SPF) rats were reared under conventional or SPF
conditions. In each group, indomethacin was given intrarectally for 2 days. Indomethacin enteropathy was evaluated using a previously
described ulcer index and tissue myeloperoxidase activity. Both
euthymic and athymic nude rats developed intestinal ulcers to the same
degree under conventional conditions but no or minimal ulcer under SPF
conditions. Pretreatment of conventional rats with intragastric
kanamycin sulfate, an aminoglycoside antibiotic, attenuated
indomethacin enteropathy in a dose-dependent fashion. Interestingly,
when lipopolysaccharide was injected intraperitoneally in
kanamycin-pretreated rats, it fully restored enteropathy in these rats
in a dose-dependent manner. We confirmed that kanamycin decreased the
number of gram-negative bacteria and endotoxin concentration of the
small intestine in a dose-dependent fashion. These results indicate
that indomethacin enteropathy is bacteria dependent and does not
require a T cell function. Synergy between indomethacin and bacterial
lipopolysaccharide may play a major role in this enteropathy.
indomethacin-induced enteropathy; T cell function; intestinal
flora; gram-negative bacteria; endotoxin
