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Tumor necrosis factor and the therapeutic potential of anti-tumor necrosis factor antibodies
J C Wherry1, J E Pennington, R P Wenzel
1Clinical Research Department, Miles Inc., Berkeley, CA 94701.
Objective:
To review the relationship of tumor necrosis factor (TNF) to clinical sepsis and the clinical potential of anti-TNF therapy in decreasing morbidity and mortality rates due to sepsis.
Data Sources:
The international English language literature was reviewed, including animal studies and human clinical trials regarding TNF, anticytokine therapy, and sepsis.
Study Selection:
Studies which characterized the immunopharmacologic interactions between TNF and sepsis were emphasized.
Data Extraction:
This study specifically focused on experiments and clinical trials that directly involve the activity of TNF or anti-TNF antibodies, particularly but not limited to data derived from septic patients.
Data Synthesis:
The relationship between TNF and sepsis is described. Clinical aspects of anti-TNF therapy (timing, empiric use) are discussed. Phase I, II, and III trail of anti-TNF antibodies in clinical trials are reviewed.
Conclusions:
Current clinical strategies for sepsis therapy are only partially effective. Recent immunopharmacologic advancements have resulted in the identification of TNF as a pivotal proinflammatory cytokine mediator of sepsis. Animal studies demonstrate that anti-TNF therapy protects animals from the morbidity and mortality of sepsis. Phase I clinical studies of anti-TNF antibodies demonstrate the safety of monoclonal antibody therapy. The therapeutic application of anti-TNF antibodies in sepsis trials is ongoing.