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.

Inhalt
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.