title: Recent advances in the pathophysiology and molecular basis of sepsis-associated organ dysfunction: Novel therapeutic implications and challenges.
abstract: Sepsis is one of the most common reasons for critically ill patients to be admitted to an intensive care unit and, despite advances in overall medical care, it represents a major clinical problem and remains the leading cause of death in the critically ill patient population. Although sepsis has been defined as a systemic inflammatory syndrome, in which there is an identifiable focus of infection, clinical trials aimed at anti-inflammatory therapeutic approaches have largely failed to identify an effective therapeutic target to improve clinical outcomes in sepsis. Very recently, the third international consensus definitions have been advocated for sepsis and septic shock. Thus, sepsis is now defined as life-threatening organ dysfunction due to a dysregulated host response to infection. A better understanding of the molecular mechanisms involved in the pathogenesis of sepsis and its resultant organ failure has been sought, and the development of therapies targeted at preventing or limiting molecular events associated with the progress of fatal organ failure, hence leading to improvement of outcomes, is urgently needed. This review article provides an overview of possible pathogenic mechanisms underlying the development of multiple organ dysfunction in sepsis and discusses pharmacological agents regarded as promising in treatment of this disorder.
authors.affiliation: Department of Molecular and Medical Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan. Electronic address: yhattori@med.u-toyama.ac.jp.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hattori
authors.affiliation: Department of Anesthesiology and Pain Relief Center, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Kohshi
authors.initials: K
authors.lastname: Hattori
authors.affiliation: Department of Molecular and Medical Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan.
authors.forename: Tokiko
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Emergency and Critical Care Medicine, Nagoya University Graduate School of Medicine, Tsuruma-cho 65, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Matsuda
mesh_terms: D000818:Animals; D017209:Apoptosis; D016207:Cytokines / Q000276:immunology; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D009102:Multiple Organ Failure / Q000188:drug therapy / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018805:Sepsis / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D016328:NF-kappa B
keywords: Apoptosis; Endothelial cells; Inflammation; Organ dysfunction; Sepsis