Editorial [ Sepsis: From the Bench to the Bedside ]

Sepsis: From the Bench to the Bedside The term sepsis derives from the Greek sepsis, which means putrefaction. The pathogenesis and clinical manifestations of sepsis result from a complex interaction between the host and the infecting microorganism. Evolving at different stages of a continuum process it places the physician before a major challenge, a medical emergency associated with high morbidity and mortality [1-3]. Despite its importance and the progress of our understanding of the sepsis pathogenesis, how to define and recognize sepsis at the bedside, and how to use similar concepts in evaluating new therapeutic strategies are still matters of debate. Bone et al. have proposed a diagnostic system based on progressive stages of the sepsis disease: bacteremia (presence of positive blood cultures); sepsis (clinical evidence suggestive of infection plus signs of a systemic response to infection); sepsis syndrome (clinical diagnosis of sepsis plus the evidence of an altered organ perfusion); and septic shock [4]. In a consensus conference sponsored of the American College of Chest Physicians and the Society of Critical Care it was recognized that a wide range of insults could lead to a similar clinical picture through common pathways. They proposed the term Systemic Inflammatory Response Syndrome (SIRS) to encompass the clinical manifestations following pancreatitis, burns, trauma and others, with the term sepsis being restricted to the SIRS triggered by infections [5, 6]. Recently, several intensive care societies revisited the definitions for sepsis and related conditions. They concluded that "the concepts of sepsis, severe sepsis, and septic shock remain useful to clinicians and researchers", and expanded the list of signs and symptoms of sepsis. They proposed, however, a developing staging system for sepsis, similar to others used in clinical medicine, stratifying patients by their baseline risk and potential to respond to therapy. The classification is called PIRO, for predisposition conditions, the nature and extend of the insult, the nature and magnitude of the host response and the degree of the organ dysfunction [7]. The pathogenesis of sepsis is a fascinating area of investigation, and our understanding of its underlying mechanisms has improved markedly in recent years [1, 8, 9], specially in bacterial recognition and cellular signaling [10,11]. Perhaps in no other disease, even infectious, are the protective and deleterious responses so closely related. Indeed, they are part of the same process, and as such may not fit into a good or bad dychotomic response. Certainly, this is an important reason for the failure of many pathogenesis-oriented target adjunctive therapies [12]. It is interesting to note that the host-response to bacteria and their products is modulated by the ongoing septic process. In this context, it has been proposed that an anti-inflammatory response should proceed the initial inflammatory response [13], or that both would occur at a different balance in different tissues [14] during sepsis. The experimental work has been fundamental for the development and testing of sepsis concepts. From the chemical studies of LPS, its biological activities, the importance of the host-response in mediating its activity, which ultimately led to discovery of the LPS-gene, much of what we know from about sepsis derives from seminal experimental work. However, a great task has been to translate the basic knowledge into the clinical setting that is, by nature, much more complex. Our therapeutic approach to sepsis has improved in the recent years. While the appropriate use of antibiotics remains the main stone of the therapy, supportive therapy has gained renewed importance and new strategies based on pathophysiology are in use nowadays. Surely, as our understanding of pathogenesis improves, new targets will be identified. It is important to emphasize the existence of a number of time-dependent interventions that reduce mortality from sepsis. A surviving sepsis campaign was launched few years ago aiming to increase awareness and improve outcome in severe sepsis, by using education and monitoring of the standards of care as strategy [15]. In this issue of the Endocrine, Metabolic & Immune Disorders " Drug Targets we aimed to provide a comprehensive overview of sepsis, from the bench to the bedside. I thank the invited authors that brought excellent reviews, mostly based on their own data, offering a wide scope of experimental and clinical work, covering the pathogenesis of sepsis and its clinical therapy. REFERENCES [1] Salomao, R.; Rigato, O.; Pignatari, A. C.; Freudenberg, M. and Galanos, C. (1999) Infection, 27, 1- 11. [2] Angus, D.C.; Linde-Zwirble, W.T.; Lidicker, J.; Clermont, G.; Carcillo, J. and Pinsky, M.R. (2001) Crit. Care Med., 29(7),1303-10. [3] Martin, G.S.; Mannino, D.M.; Eaton, S. and Moss, M. (2003) N. Engl. J. Med., 348(16),1546-54. [4] Bone, R.C. (1991) Ann. Intern. Med., 114(4), 332-3......