1. To investigate the role of endothelin in Gram-negative bacteraemia and the possible involvement of tumour necrosis factor-α 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-α) antibody.
2. Plasma immunoreactive endothelin levels were greatly increased after the Escherichia coli injection. Pre-treatment with anti-(tumour necrosis factor-α) antibody did not suppress elevated plasma immunoreactive endothelin levels (P > 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-α) antibody. Immunoreactive endothelin in spleen and kidney was undetectable (< 34 fmol/g wet weight).
4. Injection of rMu tumour necrosis factor-α 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-α.