The role of tumor necrosis factor in sepsis.
There is an increasing incidence of sepsis among hospitalized patients. Also, high mortality associated with sepsis and septic shock persists despite appropriate antibiotic therapy. Recent investigations have demonstrated that bacterial antigens stimulate a cascade of cellular mediators or cytokine release. In sepsis and septic shock the response of these cytokines often exceeds natural downregulation and leads to multisystem organ failure and even death in an unacceptably high number of patients. Many investigative studies have shown that tumor necrosis factor (TNF) is the prime mediator of the inflammatory response seen in sepsis and septic shock. Sepsis management in the future will include immune modulating therapy directed against the deleterious effects of cytokines, specifically TNF. This article reviews the current problem of sepsis and the evidence to support the role of TNF in sepsis. also, recent studies employing monoclonal antibodies against TNF as well as considerations for future studies are discussed.
Division of Infectious Diseases and Hospital Epidemiology, Henry Ford Hospital, Detroit, Michigan 48202.
C E
CE
Spooner
N P
NP
Markowitz
L D
LD
Saravolatz
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D006801:Humans; D007372:Interferons / Q000502:physiology; D007375:Interleukin-1 / Q000502:physiology; D008070:Lipopolysaccharides; D018805:Sepsis / Q000209:etiology* / Q000628:therapy; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D007372:Interferons