Am. J. Respir. Crit. Care Med., Volume 165, Number 6, March 2002, 818-823

Luteolin Reduces Lipopolysaccharide-induced Lethal Toxicity and Expression of Proinflammatory Molecules in Mice

ANASTASIA KOTANIDOU, ANGELIKI XAGORARI, ELENI BAGLI, PANAGIOTA KITSANTA, THEODORE FOTSIS, ANDREAS PAPAPETROPOULOS, and CHARIS ROUSSOS

"George P. Livanos" Laboratory, Evangelismos Hospital, Department of Critical Care and Pulmonary Services, University of Athens, Athens, Greece; and Laboratory of Biological Chemistry, Medical School, University of Ioannina, Ioannina, Greece

Luteolin is a flavonoid that has been shown to reduce proinflammatory molecule expression in vitro. In the present study, we have tested the ability of luteolin to inhibit lipopolysaccharide (LPS)- induced lethal toxicity and proinflammatory molecule expression in vivo. Mice receiving LPS (Salmonella enteriditis LPS, 32 mg/kg, intraperitoneally) exhibited high mortality with only 4.1% of the animals surviving seven days after the LPS challenge. On the contrary, mice that had received luteolin (0.2 mg/kg, intraperitoneally) before LPS showed an increased survival rate with 48% remaining alive on Day 7. To investigate the mechanism by which luteolin affords protection against LPS toxicity we measured intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor- (TNF-) production in response to LPS in the presence or absence of luteolin pretreatment. Treatment of animals with LPS increased serum TNF- levels in a time-dependent manner. The increase in peak serum TNF- levels was sensitive to luteolin pretreatment. Luteolin pretreatment also reduced LPS-stimulated ICAM-1 expression in the liver and abolished leukocyte infiltration in the liver and lung. We conclude that luteolin protects against LPS-induced lethal toxicity, possibly by inhibiting proinflammatory molecule (TNF-, ICAM-1) expression in vivo and reducing leukocyte infiltration in tissues.

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