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.