Differential induction of nitric oxide synthase in various organs of the mouse during endotoxaemia: role of TNF-alpha and IL-1-beta.
BALB/c mice injected intraperitoneally with bacterial lipopolysaccharide (LPS) developed lethal septic shock. This was accompanied by significantly elevated concentrations of nitrite and nitrate in the plasma and expression of high levels of nitric oxide (NO) synthase activity in the lungs, heart, spleen and peritoneal macrophages. Mice pretreated with anti-tumour necrosis factor-alpha (TNF-alpha) monoclonal antibody or anti-interleukin-1 beta (IL-1 beta) polyclonal antibody were protected, in a dose-dependent manner, from endotoxin-induced mortality. This effect was accompanied by a significant reduction in plasma levels of nitrite and nitrate. Antibody treatment also reduced the level of NO synthase activity in peritoneal macrophages, spleen and heart but had no effect on enzyme expression in the lung. These results demonstrate that TNF-alpha and IL-1 beta play an important role in the induction of NO following administration of LPS and in the development of endotoxin-induced shock. In addition, NO synthase activity is differentially expressed in various organs and this may not always require TNF-alpha and IL-1 beta.
Cunha
F Q
FQ
Wellcome Research Laboratories, Beckenham, Kent, U.K.
Assreuy
J
J
Moss
D W
DW
Rees
D
D
Leal
L M
LM
Moncada
S
S
Carrier
M
M
O'Donnell
C A
CA
Liew
F Y
FY
D000594:Amino Acid Oxidoreductases / Q000378:metabolism*; D000818:Animals; D004731:Endotoxins / Q000097:blood; D004926:Escherichia coli; D005260:Female; D007375:Interleukin-1 / Q000502:physiology*; D008070:Lipopolysaccharides; D008168:Lung / Q000201:enzymology; D017737:Macrophages, Peritoneal / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C; D019001:Nitric Oxide Synthase; D012772:Shock, Septic / Q000201:enzymology*; D013154:Spleen / Q000201:enzymology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D004731:Endotoxins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases