The Netherlands Journal of Medicine 2001;59:102–110 Review The role of high density lipoprotein in sepsis a,b, c c * ´ Henk J. van Leeuwen , Andre P. van Beek , Geesje M. Dallinga-Thie , b b b Jos A.G. van Strijp , Jan Verhoef , Kok P.M. van Kessel a Department of Intensive Care and Clinical Toxicology, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands b Eijkman-Winkler Institute, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands c Department of Internal Medicine, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands Received 5 June 2001; accepted 19 June 2001 Introduction response is initiated by lipopolysaccharides (LPS, endotoxin), a constituent of the outer membrane of Sepsis and septic shock are major causes of Gram negative bacteria. LPS is also found in the morbidity and mortality in intensive care units systemic circulation in the presence of sepsis caused (ICU). In the US, it has been estimated that there are by Gram positive or fungal infections [4]. LPS approximately 500 000 new episodes of sepsis, and therefore plays a pivotal role in the initiation and 200 000 cases of septic shock each year, with a perpetuation of systemic inflammation in sepsis. mortality that ranks 13th as leading cause of death In vitro lipoproteins have been found to bind LPS [1]. In the Netherlands, sepsis as the primary cause and neutralize its toxic effects [5]. In septic patients of death has risen from 3041 cases in 1990 to 3934 however the concentrations of lipoproteins, especial- cases in 1996 (CBS, personal communication). As all ly high density lipoprotein, are reduced [6] and the trials of new immunomodulating therapies for sepsis observed changes are strongly related to the severity have failed to alter the outcome of the disease, it is of the infection [7]. The pathophysiologic mecha- important to find new therapeutic options to in- nisms causing this phenomenon are unknown. The fluence the cascade of inflammatory mediators re- change in lipoprotein metabolism in sepsis may play sponsible for the clinical syndrome [2]. Recently a vital part in the perpetuation of the inflammatory activated protein C (APC) has been shown to response, as inflammation induced hypolipop- improve mortality of severe sepsis in a large mul- roteinemia reduces the LPS neutralization capacity of ticenter trial [3]. The positive result of this trial plasma which can be followed by unopposed LPS revives hope to influence the outcome in severe induced inflammation. Modulation of the lipoprotein sepsis. In Gram negative sepsis the inflammatory metabolism may influence the cascade of inflamma- tory mediators in sepsis, and may thus prevent organ failure with associated morbidity and mortality. In the following paper we will review the evidence for *Corresponding author. Tel.: 131-30-250-7330; fax: 131-30- the role of lipoproteins in LPS neutralization and in 254-1511. E-mail address: hj.van.leeuwen@rivm.nl (H.J. van Leeuwen). modulating the acute phase response in sepsis. 0300-2977 / 01 / $ – see front matter  2001 Elsevier Science B.V. All rights reserved. PII: S0300-2977(01)00144-9