title: Anti-tumor necrosis factor therapy in sepsis: update on clinical trials and lessons learned.
abstract: OBJECTIVE
  Tumor necrosis factor (TNF) is an important mediator involved in the pathogenesis of sepsis. We review clinical studies investigating the efficacy of anti-TNF therapy in decreasing mortality rates in septic patients.
  
  
  METHODS
  We conducted a computerized bibliographic search of randomized, clinical, multicenter trials studying the effects of anti-TNF therapy in the treatment of sepsis. We included all primary studies, reviewed all published meta-analyses, and contacted primary investigators of multicenter trials where necessary.
  
  
  RESULTS
  Almost all randomized studies targeting TNF during sepsis show a small, albeit nonsignificant, benefit in decreasing mortality. Strategies using monoclonal antibodies are more effective than are strategies using TNF receptor proteins. Analysis of randomized multicenter trials shows a small but significant benefit with anti-TNF therapeutic strategies. Furthermore, a recent study in 2634 septic patients using a murine anti-TNF antibody shows a 3.6% significant benefit in reducing mortality.
  
  
  CONCLUSIONS
  Anti-TNF strategies are only partially effective in patients with sepsis. Although individual studies show small, nonsignificant benefits, analysis of all trial data as well as data from a recent trial in a large population of septic patients show that anti-TNF strategies may confer a small survival benefit. Better characterization of patients and a more multimodal approach by concomitantly targeting other mediators involved in sepsis may be helpful in enlarging the clinical benefit of anti-TNF therapy.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University Hospital, Jena, Germany. Konrad.Reinhart@med.uni-jena.de
authors.forename: K
authors.initials: K
authors.lastname: Reinhart
authors.forename: W
authors.initials: W
authors.lastname: Karzai
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology / Q000627:therapeutic use; D012107:Research Design; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology* / Q000401:mortality; D016019:Survival Analysis; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; C402162:CDP 571; C427683:afelimomab