Differential induction of adrenomedullin, interleukins and tumour necrosis factor-α by lipopolysaccharide in rat tissues in vivo

1. The aim of the present study was to determine the temporal changes in tissue adrenomedullin (AM) and cytokine contents and cytokine and preproAM mRNA levels in the kidney, liver, adrenal gland and spleen of lipopolysaccharide (LPS)-treated rats. 2. Rats were injected with LPS (10 mg/kg, i.p.). Radioimmunoassay and solution hybridization-RNase protection assays were used to follow the changes in AM and its mRNA levels, respectively; ELISA and reverse transcription-polymerase chain reaction were used to follow the changes in cytokines and their mRNA levels, respectively. 3. In the kidney, the preproAM mRNA levels were increased 1 and 3 h after LPS treatment, whereas AM levels were decreased at 3 h. Interleukin (IL)-6 and IL-1 beta levels were increased at 3 and 6 h, respectively. 4. The preproAM mRNA levels were elevated in the liver 3 h after LPS injection. Concentrations of tumour necrosis factor (TNF)-alpha and IL-1 beta were increased at 1 and 6 h, respectively. 5. There were no changes in the levels of either preproAM mRNA or AM in the adrenal gland and the spleen. In the spleen, TNF-alpha levels were elevated at 1 and 3 h after LPS injection and IL-1 beta was elevated at 1 and 6 h after LPS injection, whereas in the adrenal gland IL-1 beta was elevated at 6 h after injection. 6. The mRNA levels of the three cytokines were elevated at all three time intervals examined in the kidney, liver, adrenal gland and spleen, with the exception that TNF-alpha mRNA was not elevated in the adrenal gland at 6 h after LPS injection and IL-1 beta mRNA was not elevated in the spleen at 3 and 6 h. 7. The plasma concentrations of TNF-alpha were increased at 1 and 3 h after LPS injection, whereas plasma concentration of IL-1 beta and IL-6 were elevated at 3 and 6 h for both. 8. The present results suggest that the biosynthesis and secretion of AM may be differentially regulated in various tissues of rats injected with LPS and that AM may interact with cytokines during inflammation.