title: Antibodies to cachectin/tumor necrosis factor reduce interleukin 1 beta and interleukin 6 appearance during lethal bacteremia.
abstract: Cytokines secreted in response to invading micro-organisms are important mediators of detrimental hemodynamic and metabolic changes in the host. To test whether cachectin/TNF plays a role in triggering release of other cytokines in the setting of infection, anesthetized baboons were passively immunized against systemic cachectin/TNF before infusion of a LD100 dose of live Escherichia coli. Bacteremia led to significant increases in circulating levels of cachectin/TNF, IL-1 beta, and IL-6. Although bacterial endotoxin/lipopolysaccharide is a potent stimulus for the synthesis and release of IL-1 and IL-6 in vitro, specific neutralization of cachectin/TNF in vivo with mAb pretreatment significantly attenuated both the IL-1 beta and the IL-6 responses despite fulminant overwhelming bacteremia. These data suggest that cachectin/TNF is essential for the initiation or amplification of IL-1 and IL-6 release during lethal gram-negative septic shock syndrome.
authors: Department of Surgery, New York Hospital, Cornell Medical Center, New York 10021.
authors: Y
authors: Y
authors: Fong
authors: K J
authors: KJ
authors: Tracey
authors: L L
authors: LL
authors: Moldawer
authors: D G
authors: DG
authors: Hesse
authors: K B
authors: KB
authors: Manogue
authors: J S
authors: JS
authors: Kenney
authors: A T
authors: AT
authors: Lee
authors: G C
authors: GC
authors: Kuo
authors: A C
authors: AC
authors: Allison
authors: S F
authors: SF
authors: Lowry
mesh_terms: D000818:Animals; D007116:Immunization, Passive; D007375:Interleukin-1 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D010215:Papio; D018805:Sepsis / Q000097:blood / Q000503:physiopathology*; D012772:Shock, Septic / Q000097:blood / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000502:physiology*
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha