Novel therapies for sepsis: antiendotoxin therapies
- 1 December 2002
- journal article
- review article
- Published by Informa Healthcare in Expert Opinion on Investigational Drugs
- Vol. 11 (12), 1795-1812
- https://doi.org/10.1517/13543784.11.12.1795
Abstract
Severe sepsis and septic shock is a common problem encountered in the critical care unit with an estimated incidence in the US of 750,000 cases/year and a mortality rate of 30 – 50%. Sepsis involves a complex interaction between bacterial factors and the host immune system producing a systemic inflammatory state that may progress to multiple organ failure and death. Endotoxin (a lipopolysaccharide) released from Gram-negative bacteria has been implicated as a potent, prototypical stimulus of the immune response to bacterial infection. Current antiendotoxin strategies utilise various approaches ranging from the prevention of binding to endotoxin receptors with antibodies (monoclonal or polyclonal) against endotoxin or endotoxin receptor/carrier molecules (antiCD14 or antilipopolysaccharide-binding protein antibodies), enhancing clearance or neutralisation (haemoperfusion, lipoproteins, lipopolysaccharide-neutralising proteins) or impairing cellular signalling (lipid A analogues, tyrosine kinase inhibitors). In the future, innovative therapies involving Toll-like receptors and their downstream signalling elements will be developed. This review discusses current knowledge regarding endotoxin signalling, antiendotoxin therapies currently under development, and future areas for research.Keywords
This publication has 89 references indexed in Scilit:
- Effects of continuous haemofiltration vs intermittent haemodialysis on systemic haemodynamics and splanchnic regional perfusion in septic shock patients: a prospective, randomized clinical trialNephrology Dialysis Transplantation, 2001
- Low lipid concentrations in critical illnessCritical Care Medicine, 1996
- A PHASE I SAFETY AND PHARMACOKINETIC STUDY OF A RECOMBINANT AMINO TERMINAL FRAGMENT OF BACTERICIDAL/ PERMEABILITY-INCREASING PROTEIN IN HEALTHY MALE VOLUNTEERSShock, 1996
- Inhibition of Endotoxin-Induced Cytokine Release and Neutrophil Activation in Humans by Use of Recombinant Bactericidal/Permeability-Increasing ProteinThe Journal of Infectious Diseases, 1995
- Triglyceride-rich lipoproteins improve survival when given after endotoxin in ratsSurgery, 1995
- Prevention of Lipopolysaccharide-Induced Lethal Toxicity by Tyrosine Kinase InhibitorsScience, 1994
- HA-1A in septic patients with ARDS: Results from the pivotal trialIntensive Care Medicine, 1994
- Diphosphoryl lipid A from Rhodopseudomonas sphaeroides induces tolerance to endotoxic shock in the ratCritical Care Medicine, 1993
- Structure and Function of Lipopolysaccharide Binding ProteinScience, 1990
- CD14, a Receptor for Complexes of Lipopolysaccharide (LPS) and LPS Binding ProteinScience, 1990