Adrenomedullin protected against mechanical ventilation-induced liver and gut injury in mice with pneumonia. Pneumococcal pneumonia (S.p.) was induced 24 hours before mechanical ventilation (MV) was performed for 6 hours. Continuous adrenomedullin (AM) infusion (0.05 mg/kg/hour) started with the onset of MV. Nonventilated (NV) mice were sacrificed 30 hours after infection. (A) Liver transaminases (alanine aminotransaminase (ALT), aspartate aminotransferase (AST)) were quantified in blood plasma (*P < 0.05, ***P < 0.001; n = 6 to 8 each). Liver and ileum sections were stained for cleaved caspase 3 (CC3) and counterstained with hemalaun. (B) In the MV + S.p. group, liver lobular necrosis (white arrow) surrounded by rings of CC3+ apoptotic cells (black arrow) developed, which was absent under AM treatment (MV + S.p. + AM). (C) Apoptotic CC3+ cells were observed in ileum sections of the MV + S.p. group, and to a lesser extent in the MV + S.p. + AM group. Representative images from six animals per group are shown. (D) Hematocrit (Hct) was reduced following AM treatment in ventilated mice with pneumonia (MV + S.p. + AM) as compared with sham-treated mice (MV + S.p.) (*P < 0.05; n = 5 or 6 each).