Magnolol alters cytokine response after hemorrhagic shock and increases survival in subsequent intraabdominal sepsis in rats

Magnolol is a Chinese herb that has potent antioxidant effects. This study evaluated the effect of magnolol in the treatment of severe injury using a two-hit model in Sprague-Dawley rats. Hemorrhagic shock followed by resuscitation was performed. Intra-abdominal sepsis was induced by cecal ligation puncture. The rats were randomly segregated into the following three groups: group 1 (sham group) rats were sham-operated; group 2 (untreated group) rats received hemorrhagic shock and resuscitation and cecal ligation puncture 24 h later; and group 3 (treated group) rats were treated with magnolol and subjected to the same procedures as group 2. Plasma cytokine levels and tissue cytokine contents of lung, including tumor necrosis factor alpha (TNFalpha) and interleukin (IL)-10 were assayed after hemorrhagic shock and sepsis. Pulmonary injury study was performed using Evans blue dye and survival analysis was performed after development of sepsis. Plasma and tissue TNFalpha levels increased after hemorrhagic shock. Magnolol treatment blunted the TNFalpha levels in plasma and tissue. The plasma IL-10 level increased after hemorrhagic shock, whereas the tissue level of IL-10 did not change. Magnolol treatment did not alter the plasma level of IL-10 but did increase tissue level. After sepsis, TNFalpha levels in both plasma and tissue of magnolol-treated animals were significantly lower than those in untreated animals, whereas plasma and tissue IL-10 levels were not significantly different between treated and untreated groups. Pulmonary injury study showed that magnolol-treated rats had decreased pulmonary permeability after the onset of sepsis. Survival analysis showed that survival rate was significantly higher in the treated group. In conclusion, magnolol modifies the cytokine response after hemorrhagic shock and resuscitation; the proinflammatory cytokine response is suppressed. The modified cytokines response induced by magnolol may result in decreased tissue injury and increased survival in subsequent intra-abdominal sepsis.