This review highlights the advances in the understanding of how HDL is protective in both in vitro and in vivo inflammatory settings, including the ability of HDL to modulate adhesion molecule expression, upregulate endothelial nitric oxide synthase and counteract oxidative stress. Also, the active components of HDL and the recent discovery of novel lipid modulators of inflammation are discussed.

1 Hydrogen sulfide (H 2 S) is a naturally occurring gaseous transmitter, which may play important roles in normal physiology and disease. Here, we investigated the role of H 2 S in the organ injury caused by severe endotoxemia in the rat. 2 Male Wistar rats were subjected to acute endotoxemia (Escherichia coli lipopolysaccharide (LPS) 6 mg kg À1 intravenously (i.v.) for 6 h) and treated with vehicle (saline, 1 ml kg À1 i.v.) or DLpropargylglycine (PAG, 10-100 mg kg À1 i.v.), an inhibitor of the H 2 S-synthesizing enzyme cystathionine-g-lyase (CSE). PAG was administered either 30 min prior to or 60 min after the induction of endotoxemia. 3 Endotoxemia resulted in circulatory failure (hypotension and tachycardia) and an increase in serum levels of alanine aminotransferase and aspartate aminotransferase (markers for hepatic injury), lipase (indicator of pancreatic injury) and creatine kinase (indicator of neuromuscular injury). In the liver, endotoxemia induced a significant increase in the myeloperoxidase (MPO) activity, and in the expression and activity of the H 2 S-synthesizing enzymes CSE and cystathionine-b-synthase. 4 Administration of PAG either prior to or after the injection of LPS dose-dependently reduced the hepatocellular, pancreatic and neuromuscular injury caused by endotoxemia, but not the circulatory failure. Pretreatment of rats with PAG abolished the LPS-induced increase in the MPO activity and in the formation of H 2 S and in the liver. 5 These findings support the view that an enhanced formation of H 2 S contributes to the pathophysiology of the organ injury in endotoxemia. We propose that inhibition of H 2 S synthesis may be a useful therapeutic strategy against the organ injury associated with sepsis and shock.