Tumor necrosis factor: an updated review of its biology.

OBJECTIVE: To review the role of tumor necrosis factor (TNF) in the pathogenesis of the septic shock syndrome. DATA SOURCES: The international English language literature from 1985 to present formed the basis for this review. MEDLINE was used to identify pertinent animal and human studies pertaining to the clinically relevant aspects of TNF and related cytokines. STUDY SELECTION: Those studies that focused on developments that may lead to advances in the therapy for septic shock syndrome were emphasized. Investigations that described in vivo and human results served as the primary database. DATA EXTRACTION: Animal studies were selected based on the similarity of the model pathogenesis and outcomes to the human clinical sepsis syndrome. Patient studies were selected on the basis of study design and sample size. DATA SYNTHESIS: The normal role of TNF and pathologic effects consequent to the excessive production of TNF in response to an overwhelming infection or injury are reviewed. Evidence establishes the role of TNF in septic shock syndrome. Novel therapies, such as anti-TNF monoclonal antibodies, soluble TNF receptors, or soluble TNF receptor-immunoglobulin G heavy chain fusion proteins, may confer protection against septic shock syndrome.
CONCLUSIONS: TNF plays a major role in the pathogenesis of the septic shock syndrome. TNF exerts a range of beneficial and injurious effects that may ultimately lead to organ dysfunction and death. The burst of TNF release after endotoxemia promotes the progression of the shock syndrome even in the absence of further TNF release. New therapies targeted to the attenuation of TNF may hold promise for the management of patients with septic shock syndrome.