TUMOR-NECROSIS-FACTOR AND THE THERAPEUTIC POTENTIAL OF ANTITUMOR NECROSIS FACTOR ANTIBODIES

Objective: To review the relationship of tumor necrosis factor (TNF) t o clinical sepsis and the clinical potential of anti-TNF therapy in de creasing morbidity and mortality rates due to sepsis. Data Sources: Th e international English language literature was reviewed, including an imal studies and human clinical trials regarding TNF, anticytokine the rapy, and sepsis. Study Selection: Studies which characterized the imm unopharmacologic interactions between TNF and sepsis were emphasized. Data Extraction: This study specifically focused on experiments and cl inical trials that directly involve the activity of TNF or anti-TNF an tibodies, particularly but not limited to data derived from septic pat ients. Data Synthesis: The relationship between TNF and sepsis is desc ribed. Clinical aspects of anti-TNF therapy (timing, empiric use) are discussed. Phase I, II, and III trials of anti-TNF antibodies in clini cal trials are reviewed. Conclusions: Current clinical strategies for sepsis therapy are only partially effective. Recent immunopharmacologi c advancements have resulted in the identification of TNF as a pivotal proinflammatory cytokine mediator of sepsis. Animal studies demonstra te that anti-TNF therapy protects animals from the morbidity and morta lity of sepsis. Phase I clinical studies of anti-TNF antibodies demons trate the safety of monoclonal antibody therapy. The therapeutic appli cation of anti-TNF antibodies in sepsis trials is ongoing.