Novel pharmacologic approaches to the management of sepsis: targeting the host inflammatory response.
Sepsis is currently the 10(th) leading cause of death overall and accounts for significant healthcare expenditures in the developed world. There are now more deaths attributable to sepsis than coronary artery disease, stroke, or cancer, and it is widely believed that the incidence of sepsis and sepsis-related mortality will continue to rise. Based on these sobering statistics, there is great interest in identifying novel treatments for managing critically ill children and adults with sepsis. Unfortunately, to date, there have been very few successful therapeutic agents employed in the clinical setting. Despite these disappointing results, new therapeutic agents continue to be identified, and there is reason for optimism and hope for the future. Herein, we will briefly review several novel therapeutic adjuncts for the management of critically ill patients with sepsis. We will largely focus on those therapies that directly target the host inflammatory response, specifically those that result in activation of the transcription factor, nuclear factor (NF)-kappaB. We will also reference some of the patents recently filed that pertain to the host innate immune response and sepsis.
Wheeler
Derek S
DS
Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229-3039, USA. Derek.wheeler@cchmc.org
Zingarelli
Basilia
B
Wheeler
William J
WJ
Wong
Hector R
HR
D000209:Acute-Phase Proteins / Q000627:therapeutic use; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D023181:Antimicrobial Cationic Peptides / Q000627:therapeutic use; D002352:Carrier Proteins / Q000627:therapeutic use; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007155:Immunologic Factors / Q000627:therapeutic use; D018950:Lipopolysaccharide Receptors / Q000627:therapeutic use; D008075:Lipoproteins, HDL / Q000627:therapeutic use; D008562:Membrane Glycoproteins / Q000627:therapeutic use; D016328:NF-kappa B / Q000276:immunology* / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology* / Q000378:metabolism; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D023181:Antimicrobial Cationic Peptides; D002352:Carrier Proteins; D016207:Cytokines; D007155:Immunologic Factors; D018950:Lipopolysaccharide Receptors; D008075:Lipoproteins, HDL; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D051193:Toll-Like Receptors; D000099231:Lipopolysaccharide-Binding Protein