Cytokine modulation in sepsis and septic shock.
Sepsis and septic shock are a major cause of morbidity and mortality in patients admitted to the intensive care unit. Since the introduction of antibiotic therapy, the mortality associated with sepsis has remained within the 30- 50% range. Sepsis constitutes the systemic response to infection. This response encompasses both pro-inflammatory and anti-inflammatory phases that are marked by the sequential generation of pro- and anti-inflammatory cytokines. Among the most important pro-inflammatory cytokines are TNF-alpha and IL-1beta. The pro-inflammatory effects of such cytokines are inhibited by soluble receptors/receptor antagonists and anti-inflammatory cytokines including IL-10 and transforming growth factor-beta. Modulation of the activity of both pro- and anti-inflammatory cytokines to improve outcome in patients with sepsis has been subject of multiple clinical studies. This review will examine clinical trials evaluating several strategies for blocking or attenuating TNF-alpha and IL-1beta activity. This review will also survey the current state of experimental therapies involving IL-10, transforming growth factor-beta, granulocyte colony-stimulating factor and IFN-phi. Finally, newer developments related to less known cytokines such as macrophage migration inhibitory factor and high mobility group 1 protein will be evaluated.
Zanotti
Sergio
S
Section of Critical Care Medicine, Rush-Presbyterian-St. Luke's Medical Center, Room 214 Jones, 1635 west Congress Parkway, Chicago, Illinois 60612, USA. szanotti@rush.edu
Kumar
Aseem
A
Kumar
Anand
A
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D006801:Humans; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D012772:Shock, Septic / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D016207:Cytokines