title: The proinflammatory cytokines interleukin-1 and tumor necrosis factor and treatment of the septic shock syndrome.
abstract: Treating the septic shock syndrome with antibodies that block only endotoxin has its limitations. Other targets for treating septic shock include neutralizing antibodies to the complement fragment C5a, platelet-activating factor antagonists, and blockade of endothelial cell leukocyte adhesion molecules. Specific blockade of the proinflammatory cytokines interleukin-1 (IL-1) or tumor necrosis factor (TNF) reduces the morbidity and mortality associated with septic shock. Moreover, blocking IL-1 and TNF likely has uses in treating diseases other than septic shock. Use of neutralizing antibodies to TNF or to IL-1 receptors have reduced the consequences of infection and inflammation, including lethal outcomes in animal models. The IL-1 receptor antagonist, a natural-occurring cytokine, blocks shock and death due to Escherichia coli and ameliorates a variety of inflammatory diseases. Soluble TNF and IL-1 surface receptors, which bind their respective cytokines, also ameliorate disease processes. Current clinical trials are evaluating the safety and efficacy of these anticytokine therapies either alone or together.
authors.affiliation: Department of Medicine, Tufts University, Boston, Massachusetts.
authors.forename: C A
authors.initials: CA
authors.lastname: Dinarello
mesh_terms: D005786:Gene Expression Regulation; D006801:Humans; D007116:Immunization, Passive; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D012772:Shock, Septic / Q000209:etiology / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000502:physiology*
chemical_list: D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha