Toll-like receptor 4 modulation as a strategy to treat sepsis.
Despite a decrease in mortality over the last decade, sepsis remains the tenth leading causes of death in western countries and one of the most common cause of death in intensive care units. The recent discovery of Toll-like receptors and their downstream signalling pathways allowed us to better understand the pathophysiology of sepsis-related disorders. Particular attention has been paid to Toll-like receptor 4, the receptor for Gram-negative bacteria outer membrane lipopolysaccharide or endotoxin. Since most of the clinical trial targeting single inflammatory cytokine in the treatment of sepsis failed, therapeutic targeting of Toll-like receptor 4, because of its central role, looks promising. The purpose of this paper is to focus on the recent data of various drugs targeting TLR4 expression and pathway and their potential role as adjunctive therapy in severe sepsis and septic shock.
Wittebole
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X
Critical Care Unit, Acute Medicine Department, St Luc University Hospital, Université Catholique de Louvain, Avenue Hippocrate 10, 1200 Bruxelles, Belgium. xavier.wittebole@uclouvain.be
Castanares-Zapatero
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Laterre
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PF
D000700:Analgesics / Q000627:therapeutic use; D000701:Analgesics, Opioid / Q000627:therapeutic use; D000818:Animals; D000906:Antibodies / Q000276:immunology; D018501:Antirheumatic Agents / Q000627:therapeutic use; D002738:Chloroquine / Q000627:therapeutic use; D002762:Cholecalciferol / Q000031:analogs & derivatives / Q000627:therapeutic use; D004187:Disaccharides / Q000627:therapeutic use; D005731:Ganglionic Stimulants / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007649:Ketamine / Q000627:therapeutic use; D051218:Lymphocyte Antigen 96 / Q000276:immunology; D009538:Nicotine / Q000627:therapeutic use; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology; D013403:Sugar Phosphates / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000627:therapeutic use*
D000700:Analgesics; D000701:Analgesics, Opioid; D000906:Antibodies; D018501:Antirheumatic Agents; D004187:Disaccharides; D005731:Ganglionic Stimulants; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C495377:LY96 protein, human; D051218:Lymphocyte Antigen 96; D013403:Sugar Phosphates; D013449:Sulfonamides; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; C507035:ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylate; D002762:Cholecalciferol; C512420:eritoran; D007649:Ketamine; D009538:Nicotine; D002738:Chloroquine
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