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Histamine Scavenging Attenuates Endotoxin-Induced Acute Lung Injury
aCNRS Institute Transgenose, IEM, Orleans, France, and IIDMM, UCT, Cape Town, South Africa bCentre for Ecology and Hydrology, Oxford, England cKey-Obs S. A., Orleans, France dEvolutec Ltd., Green Park, England
Address for correspondence. B. Ryffel, 3B rue de La Ferollerie, F-45071 Orleans, France. Voice: +33 238 25 54 38; fax: +33 238 25 79 79. bryffel{at}cnrs-orleans.fr
Histamine is an important mediator of early and late inflammatory responses. Here we asked whether scavenging of endogenous histamine by the arthropod-derived histamine binding protein EV131 diminishes acute respiratory distress syndrome (ARDS) induced by inhaled endotoxin. We demonstrate that EV131 (360 µg given intranasally) reduced endotoxin-induced bronchoconstriction and recruitment of neutrophils. Furthermore, EV131 administration diminished TNF-
 and protein leak in the bronchoalveolar lavage fluid. The data suggest that histamine attenuates endotoxin-induced bronchoconstriction and neutrophil recruitment. Therefore, scavenging of histamine by EV131 may represent a novel therapeutic strategy in ARDS.
Key Words: endotoxin • acute respiratory distress syndrome (ARDS) • histamine scavenging • mice
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