Antibodies to cachectin/tumor necrosis factor reduce interleukin 1 beta and interleukin 6 appearance during lethal bacteremia.
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.
Fong
Y
Y
Department of Surgery, New York Hospital, Cornell Medical Center, New York 10021.
Tracey
K J
KJ
Moldawer
L L
LL
Hesse
D G
DG
Manogue
K B
KB
Kenney
J S
JS
Lee
A T
AT
Kuo
G C
GC
Allison
A C
AC
Lowry
S F
SF
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*
D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha