ADMINISTRATION OF LOW-DOSE LIPOPOLYSACCHARIDE INDUCES HELLP-LIKE SYNDROME (HEMOLYSIS, ELEVATED LIVER-ENZYMES AND LOW PLATELETS) IN PREGNANTRATS - INVOLVEMENT OF MACROPHAGES IN ITS PATHOGENESIS

HELLP syndrome (hemolysis, elevated liver enzymes and low platelets) i s one of serious complications of human pregnancy, but its pathogenesi s is poorly understood. The present study has revealed that intravenou s administration of low-dose (0.2mg/kg b.w.) of lipopolysaccharide (LP S) into pregnant rats induces laboratory and histopathologic abnormali ties similar to those of human HELLP syndrome. Histological lesions we re restricted to the liver and did not include distinctive features of disseminated intravascular coagulation (DIC) such as renal cortical n ecrosis. Prominent fibrin deposits were seen along the hepatic sinusoi ds, followed by the confluent hepatic necrosis in the periportal zone. During pregnancy, liver macrophages increased in number. Blockade of liver macrophages by gadolinium chloride prevented the development of HELLP-like syndrome in LPS-treated pregnant rats without lowering the plasma level of tumor necrosis factor-alpha (TNF-alpha). Hysterectomy performed immediately before LPS injection did not decrease the matern al mortality nor reduce the liver injury. These results indicate that primed liver macrophages induced during pregnancy are responsible for the development of LPS-induced HELLP-like syndrome in rats and that th e contribution of TNF-alpha or substances present in the fete-placenta l unit to the pathogenesis may be slight.