Endothelin immunoreactivity in mice with gram-negative bacteraemia: relationship to tumour necrosis factor-alpha.
1. To investigate the role of endothelin in Gram-negative bacteraemia and the possible involvement of tumour necrosis factor-alpha in its pathophysiology, we measured plasma and tissue (lung, kidney and spleen) immunoreactive endothelin levels in Gram-negative bacteraemic mice, with and without passive immunization by anti-(tumour necrosis factor-alpha) antibody. 2. Plasma immunoreactive endothelin levels were greatly increased after the Escherichia coli injection. Pretreatment with anti-(tumour necrosis factor-alpha) antibody did not suppress elevated plasma immunoreactive endothelin levels (P greater than 0.1). 3. Lung tissue immunoreactive endothelin levels in mice were increased 16 h after the E. coli injection and were not affected by prior passive immunization with anti-(tumour necrosis factor-alpha) antibody. Immunoreactive endothelin in spleen and kidney was undetectable (less than 34 fmol/g wet weight). 4. Injection of rMu tumour necrosis factor-alpha into mice did not increase plasma immunoreactive endothelin levels. 5. Antibody to endothelin given 30 min after a 90% lethal dose challenge with E. coli did not affect mortality. 6. We conclude that the rise in plasma and tissue endothelin that occurs in Gram-negative bacteraemia is independent of tumour necrosis factor-alpha.
Takahashi
K
K
Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London.
Silva
A
A
Cohen
J
J
Lam
H C
HC
Ghatei
M A
MA
Bloom
S R
SR
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D016232:Endothelins / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism; D004927:Escherichia coli Infections / Q000378:metabolism*; D007116:Immunization, Passive; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D016232:Endothelins; D014409:Tumor Necrosis Factor-alpha