ENDOGENOUS BACTERIAL TOXINS ARE REQUIRED FOR THE INJURIOUS ACTION OF PLATELET-ACTIVATING-FACTOR IN RATS

Background & Aims: platelet-activating factor (PAF), an endogenous med iator for experimental sepsis, has been shown to induce shock and inte stinal 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 t he role of endogenous bacterial products, such as endotoxin, in PAF-in duced intestinal injury. Methods: PAF (3 mu g/kg) was injected intrave nously into normally colonized rats, germfree rats, and normal rats pr etreated with a combination of antibiotics, and the systemic response and intestinal injury were assessed. Results: PAF did not cause prolon ged shock, leukopenia, hemoconcentration, and bowel necrosis in germfr ee rats. When germfree rats were primed with a low dose (0.5 mg/kg) of endotoxin, the protection was lost. Combined treatment of the normall y colonized rats with neomycin, polymyxin B, and metronidazole for 7 d ays largely protected the animal from PAF-induced shock and intestinal necrosis. Conclusions: PAF does not directly induce prolonged hypoten sion, hemoconcentration, persistent leukopenia, and gross intestinal n ecrosis but causes these changes via a synergism with endogenous bacte rial toxins, presumably from the gut flora.