Adrenomedullin expression and cytokine response in experimentally induced endotoxaemia

Abstract

BACKGROUND: Adrenomedullin (AM) is a potent vasodilatory peptide involved in cardiovascular homeostasis and in inflammation. To study the effect of septicaemia, we examined the temporal changes in tissue AM and preproAM mRNA levels, and cytokine response in a rat model of endotoxaemia. METHOD: Male Sprague–Dawley rats received intraperitoneal injection of lipopolysaccharide (LPS) at 10 mg/kg weight, or saline as control. Rats were sacrificed at 1, 3, 6, 12 and 24 h after injection. Concentrations of AM and proinflammatory cytokines (TNF-a, IL-1b and IL-6) in the plasma and various tissues were measured. PreproAM mRNA levels were determined using solution hybridization-RNase protection assay. RESULTS: Plasma AM was raised at 3, 6, and 12 h. There were significant increases in preproAM mRNA levels in the lung at 3 and 6 h, in the liver at 3 h, and in the kidney at 1 and 3 h; while there was no change in preproAM mRNA levels in the spleen and adrenal gland. Immunoreactive AM concentration was increased in the lung at 3, 6, and 12 h, but not changed in the liver or the kidney. Concentrations of TNF-a were raised in the plasma at 1, 3 and 6 h, in the lung at 1 h, in the spleen at 1–3 h, and the liver at 1 h. Concentrations of IL-1b were increased in the plasma at 3 and 6 h, in the lung at 3–12 h, in the spleen at 1–12 h, and the kidney at 6 h. Concentrations of IL-6 were increased in the plasma at 3–12 h. However, there was no significant change in IL-6 levels in the tissue extracts tested. CONCLUSIONS: Endotoxin stimulates the expression of AM and proinflammatory cytokines in systemic circulatory and localized tissues. AM may be involved in the systemic response to sepsis.