Role of platelet activating factor in necrotizing enterocolitis development in the rat

Platelet activating factor (PAF) has been reported to play a role in the de velopment of necrotizing enterocolitis of the newborn. In an adult rat necr otizing enterocolitis model, pretreatment with recombinant human PAF acetyl hydrolase (r-PAF-AH) completely protected the animals against necrotizing e nterocolitis development. The protection was dose- and time-dependent. The plasma PAF-AH activity required for necrotizing enterocolitis prevention wa s similar to that previously observed following dexamethasone administratio n. The administration of a non-hydrolyzable analog of PAF, cPAF, generated necrotizing enterocolitis which was not altered by the administration of r- PAF-AH. The administration of low doses of lipopolysaccharide (LPS) in comb ination with tumor necrosis factor-or or high doses of LPS alone caused a s evere hemorrhage of the lamina propria of the intestine. The hemorrhagic le sions were similar to those observed with necrotizing enterocolitis. In bot h cases necrosis was not observed. The administration of r-PAF-AH prevented the hemorrhagic infiltration and the intestine appeared to be normal as ju dged by both gross and microscopic examination. When PAF and LPS were injec ted intraperitoneally, necrotizing enterocolitis developed in approximately 80% of the animals. Again, pretreatment with r-PAF-AH completely protected against necrotizing enterocolitis development. These findings provide furt her evidence for the central role of PAF in the development of necrotizing enterocolitis and a possible mechanism for the treatment of necrotizing ent erocolitis is suggested.