Anti-tumor necrosis factor therapy in sepsis: update on clinical trials and lessons learned

Crit Care Med. 2001 Jul;29(7 Suppl):S121-5. doi: 10.1097/00003246-200107001-00037.


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.

Data sources: 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.

Data synthesis: 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.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use
  • Humans
  • Receptors, Tumor Necrosis Factor / immunology
  • Receptors, Tumor Necrosis Factor / therapeutic use
  • Research Design
  • Sepsis / drug therapy*
  • Sepsis / immunology*
  • Sepsis / mortality
  • Survival Analysis
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Antibodies, Monoclonal
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • CDP 571
  • afelimomab