Tumor necrosis factor in the pathogenesis of infectious diseases

OBJECTIVES: To review the immunologic role of the cytokines and the specific role that tumor necrosis factor (TNF) plays in response to infection. The influence of bacterial lipopolysaccharide on TNF, the cytokine cascade, and resultant pathologies are also reviewed. DATA SOURCES: A MEDLINE search of the international English language literature from 1960 to the present was reviewed, but data from the past 5 yrs primarily formed the basis for this review. STUDY SELECTION: Those studies detailing the interaction of lipopolysaccharide, TNF, and other cytokines, and their roles in combating infection were emphasized. Investigations that described animal and human results served as the primary database. DATA EXTRACTION: Animal studies were selected based on the relevance of the model to the pathogenesis of the human clinical syndrome. Where they provided supportive evidence, patient studies were selected on the basis of study design. DATA SYNTHESIS: TNF plays a key role in the normal immune response to infection, limiting the spread of pathogens. Exaggerated physiologic responses occur under the influence of high concentrations of TNF that are released in response to overwhelming infection, resulting in aberrations in coagulation, cell adhesion, chemotaxis/transmigration, and vascular integrity. These pathologic effects may be inhibited by anti-TNF monoclonal antibodies and recombinant soluble receptor inhibitory proteins. CONCLUSIONS: TNF exerts both physiologic and pathologic effects in response to infection; these events may lead to organ dysfunction and death. Anti-TNF therapies appear to attenuate the injurious effects of TNF.