Adipocytokines in Severe Sepsis and Septic Shock

Among the different conditions of critical illness leading to admission to an Intensive Care Unit (ICU), sepsis remains the leading cause of death at the non-coronary medical ICU [1]. Even with optimal therapy, mortality rates of severe sepsis and septic shock are about 40 to 50% [2, 3]. Although there are numerous studies with varying methods from different countries, the incidence of severe sepsis is constantly approximately one out of ten admissions to all ICUs worldwide [4]. With millions of individuals concerned every year, worldwide sepsis is one of the major healthcare problems today. The proportion of severe sepsis, and case fatal outcomes increased during the last years [2]. It is crucial to establish the diagnosis sepsis as early as possible and to identify its origin, in order to initiate an appropriate therapy permitting to achieve the best possible outcome [5]. Sepsis is defined as a systemic inflammatory response syndrome (SIRS) caused by an infection. The association with organ dysfunction or sepsis-induced hypotension is termed severe sepsis. Septic shock, as a subset of severe sepsis, is characterized by sepsis-induced hypotension, persisting despite adequate fluid resuscitation [6]. Early differentiation between sepsis and SIRS is a considerable problem in the treatment of patients on ICU. Due to the early systemic release of inflammatory cytokines as compared with synthesis of acutephase-proteins, cytokines have been widely investigated for their diagnostic potential in predicting sepsis [7]. Nevertheless, until now the perfect biomarker for differentiation of sepsis and SIRS has not been found yet and ongoing research focuses on identification of appropriate diagnostic biomarkers for sepsis [8]. Despite a growing number of studies, the physiopathology of sepsis is not satisfyingly understood. Data show that physiopathology is characterized by a large number of proand anti-inflammatory cytokines and mediators of inflammation with complex interactions [9]. For instance, the application of a single bolus i.v. infusion of endotoxin to a healthy individual leads to the expression of 3147 genes, (> 10% of the human genome) [10]. These mediators and cytokines lead to endothelial dysfunction and activation of inflammatory and coagulation pathways as reaction to the invasion of a pathogen [11]. In order to reduce the sepsis-related high mortality, a better understanding of common pathogenic mechanisms of sepsis and other critical diseases is needed, potentially resulting in more effective treatment options.