TUMOR-NECROSIS-FACTOR IN THE PATHOGENESIS OF INFECTIOUS-DISEASES

Objectives: To review the immunologic role of the cytokines and the sp ecific role that tumor necrosis factor (TNF) plays in response to infe ction. The influence of bacterial lipopolysaccharide on TNF, the cytok ine cascade, and resultant pathologies are also reviewed. Data Sources : A MEDLINE search of the international English language literature fr om 1960 to the present was reviewed, but data from the past 5 Yrs prim arily formed the basis for this review. Study Selection: Those studies detailing the interaction of lipopolysaccharide, TNF, and other cytok ines, and their roles in combating infection were emphasized. Investig ations that described animal and human results served as the primary d atabase. Data Extraction: Animal studies were selected based on the re levance of the model to the pathogenesis of the human clinical syndrom e. Where they provided supportive evidence, patient studies were selec ted on the basis of study design.Data Synthesis: TNF plays a key role in the normal immune response to infection, limiting the spread of pat hogens. Exaggerated physiologic responses occur under the influence of high concentrations of TNF that are released in response to overwhelm ing infection, resulting in aberrations in coagulation, cell adhesion, chemo-taxis/transmigration, and vascular integrity. These pathologic effects may be inhibited by anti-TNF monoclonal antibodies and recombi nant soluble receptor inhibitory proteins. Conclusions: TNF exerts bot h physiologic and pathologic effects in response to infection; these e vents may lead to organ dysfunction and death. Anti-TNF therapies appe ar to attenuate the injurious effects of TNF.