Cytokines in Severe Sepsis and Septic Shock

ISBN-13: 9783034897594 / Angielski / Miękka / 2012 / 372 str.

H. Redl

Opis

t Heinz Red and Gunther Sch ag Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria The word "sepsis" derives from the Greek meaning decay or rottenness. Tradition- ally this term has been used to describe the process of infection accompanied by the host's systemic inflammatory response. Based on that understanding, previous clin- ical studies have been designed to include only patients with positive blood cultures 1, 2]. However, the frequent occurrence of a septic response without the demon- stration of microorganisms in the circulation has led to a new definition and under- standing of sepsis, mainly as the systemic response of the host to an often unde- tectable microbiological or non-microbiological process 3]. The general consensus is that cytokines are central to the inflammatory response, particularly in sepsis. It is now known that not only Gram-negative but also Gram- positive, viral, and fungal infections initiate the complex cascades of cytokine release. Probably the most important aspect of bacterial action is the release of toxic bacterial products. In particular endotoxin from Gram-negative bacteria (see chap- ter by Schade) and super antigens (see chapter by Neumann and Holzmann), as well as pore-forming toxins 4] from Gram-positive bacteria, induce cytokine formation. The importance of this cytokine release is evident from both diagnostic and thera- peutic (mostly experimental) studies, and the action of cytokines may be the key to our understanding of the pathophysiology of the sepsis syndrome.

Spis treści

Induction.- Inducers.- Endotoxin as an inducer of cytokines.- Acute lung inflammation in septic shock of the cytokine release induced by bacterial superantigens.- Lipopolysaccharide signaling pathways and their role in the development of the systemic inflammatory response syndrome.- Predisposing factors.- Predisposing factors: Effect of sex, nutritional factors and age on immunity following shock and sepsis.- Genetics: Cytokine polymorphisms.- Diagnostic.- Possibilities and problems of cytokine measurements.- Soluble TNF receptors.- Relevance of surrogate tests in intensive care patiens or “Heisenberg at the ICU”.- Actions (selected events).- Nitric oxide and endothelin-1 in circulatory shock involving cytokines.- Multistep processes in neutrophil homotypic aggregation and tissue injury.- Cytokines, coagulation and fibrinolysis.- Apoptosis: Its role in the systemic inflammatory response syndrome and the involvement of cytokines.- Importance of cytokine metabolism for malnutrition, catabolism and endocrinological state in sepsis.- Therapy.- Endotoxin scavengers as a therapeutic strategy for sepsis.- Interfering with the production of cytokines in sepsis.- Neutralizing antibodies and receptor constructs.- Immunomodulation following shock and sepsis.- Gene therapy — an alternative approach for anti-cytokine therapies.- The failure of clinical trials in sepsis.- The failure of clinical trials in sepsis: Challenges of pre-clinical models.- The failure of clinical trials in sepsis: Challenges of clinical trial design.