Lipo prostaglandin E1 reduces the production of CXC chemokines in endotoxin-induced rat liver injury

The present study attempted to assess the effect of prostaglandin El (PGE1) incorporated into lipid microspheres (Lipo PGE1) on chemokine production i n endotoxin-induced rat liver injury. Male Wistar rats weighing 200-250 g w ere injected with 2 mg lipopolysaccharide (LPS) per kg intravenously. Lipo PGE1 was administered simultaneously at various concentrations (0.002. 0.02 , 0.2, 2 mug/kg) in the tail vein. Blood samples and liver specimens were t aken from the rats at 1, 3, 8. 12 and 24 h after injection with LPS alone o r with LPS and Lipo PGE1. Serum macrophage inflammatory protein-2 (MIP-2) a nd cytokine-induced neutrophil chemoattractant (CINC) levels were measured by the enzyme-linked immunosorbant assay using the corresponding antibodies . Liver specimens were fixed, and the number of neutrophils that had infilt rated each liver section was determined under a microscope. Serum alanine a minotransferase (ALT) levels were significantly lower in the rats injected with LPS and Lipo PGE1 compared with those in the rats injected with LPS al one, and this difference was expressed in a PGE1 dose-dependent manner. Ser um MIP-2 levels were significantly lower at 3 h (141.4 +/- 95.5 pg/ml) and 8 h (44.9 +/- 34.7 pg/ml) after injection with LPS and Lipo-PGE1 (2 mug/kg) than at the same times after injection with LPS alone (342.9 +/- 35.9 and 358.3 +/- 23.4 pg:ml, respectively). Similarly, serum CINC levels were sign ificantly lower at 8 h (482.7 +/- 156.0 ng/ml) after injection with LPS and Lipo-PGE1 (2 mug/kg) than at the same time after injection LPS alone (723. 3 +/- 29.0 ng/ml). No significant differences were observed at any time bet ween serum tumor necrosis factor-alpha (TNF-alpha) levels in rats injected with LPS alone and in rats injected with LPS and Lipo-PGE1 (2 mug/kg). The number of neutrophils that had infiltrated the liver was significantly lowe r at 8 h after injection with LPS and Lipo PGE1 than at the same time after injection with LPS alone. This difference was expressed in a Lipo PGE1 dos e-dependent manner. In conclusion, Lipo PGE1 reduces liver injury and serum levels of MIP-2 and CINC, bur not TNF-alpha, in rats injected with LPS and also reduces the number of neutrophils that infiltrate in the liver. (C) 2 001 Elsevier Science Ireland Ltd. All rights reserved.