Mepacrine but not Methylprednisolone Decreases Acute Edematous Lung Injury after Injection of Phorbol Myristate Acetate in Rabbits1,2

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Abstract
A good model of the adult respiratory distress syndrome (ARDS) is intravenously injected phorbol myristate acetate (PMA), which causes pulmonary sequestration of neutrophils and a neutrophil-dependent acute edematous lung injury in rabbits. In the present study, pretreatment of rabbits with the antimalarial agent, mepacrine, prevented lung edema after injection of PMA without altering initial accumulations of neutrophils in the lung. Mepacrine also decreased oxygen radical production and degranulation by neutrophils stimulated by PMA in vitro. In contrast, pretreatment with methylprednisolone did not decrease edematous lung injury in rabbits given PMA nor did it inhibit 02 radical production or degranulation by neutrophils treated with PMA in vitro. Our results suggest that agents that modify neutrophil function may be useful in de creasing lung injury after PMA treatment and, perhaps, in treating patients with ARDS.