Endogenous bacterial toxins are required for the injurious action of platelet-activating factor in rats.
OBJECTIVE
Platelet-activating factor (PAF), an endogenous mediator for experimental sepsis, has been shown to induce shock and intestinal necrosis in vivo. However, it is unclear whether PAF exerts its injurious effects on the intestinal tissue directly or via synergism with other endogenous products. The aim of this study was to examine the role of endogenous bacterial products, such as endotoxin, in PAF-induced intestinal injury.


METHODS
PAF (3 micrograms/kg) was injected intravenously into normally colonized rats, germfree rats, and normal rats pretreated with a combination of antibiotics, and the systemic response and intestinal injury were assessed.


RESULTS
PAF did not cause prolonged shock, leukopenia, hemoconcentration, and bowel necrosis in germfree rats. When germfree rats were primed with a low dose (0.5 mg/kg) of endotoxin, the protection was lost. Combined treatment of the normally colonized rats with neomycin, polymyxin B, and metronidazole for 7 days largely protected the animal from PAF-induced shock and intestinal necrosis.


CONCLUSIONS
PAF does not directly induce prolonged hypotension, hemoconcentration, persistent leukopenia, and gross intestinal necrosis but causes these changes via a synergism with endogenous bacterial toxins, presumably from the gut flora.
Sun
X M
XM
Department of Pathology, Children's Memorial Hospital, Chicago, Illinois.
MacKendrick
W
W
Tien
J
J
Huang
W
W
Caplan
M S
MS
Hsueh
W
W
D000704:Analysis of Variance; D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism*; D004359:Drug Therapy, Combination / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology; D007422:Intestines / Q000473:pathology; D008297:Male; D008795:Metronidazole / Q000494:pharmacology; D009336:Necrosis; D009355:Neomycin / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000008:administration & dosage / Q000502:physiology*; D011112:Polymyxin B / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012769:Shock / Q000209:etiology / Q000517:prevention & control; D013047:Specific Pathogen-Free Organisms
D001427:Bacterial Toxins; D004731:Endotoxins; D010972:Platelet Activating Factor; D008795:Metronidazole; D009355:Neomycin; D011112:Polymyxin B