Günther Schlag

Cytokines in severe sepsis and septic shock

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.

Successful Administration of the NO Synthase Inhibitor 546C88 as a Delayed Continuous Infusion in a Baboon Model of Septic Shock

Nitric oxide (NO) as both a vasodilator and under certain circumstances a cyto-toxic molecule is suggested as one of the critical mediators of severe sepsis and septic shock. Whether NO is really a central molecule in sepsis and whether inhibition/scavenging has more beneficial or detrimental effects are, however, controversial questions with conflicting data. Many studies demonstrate either one or both effects; these have been thoroughly reviewed recently [1].