Tumor necrosis factor and the therapeutic potential of anti-tumor necrosis factor antibodies.

ABSTRACT

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.