Effect of methylprednisolone on phospholipase A(2) activity and lung surfactant degradation in acute lung injury in rabbits.
Glucocorticoids are the most potent and widely used anti-inflammatory agents, but they are not particularly effective against early phase of acute respiratory distress syndrome. We investigated whether methylprednisolone, a synthetic glucocorticoid, could inhibit increase of phospholipase A(2) activity in the lung and lead to protection against a model of acute respiratory distress syndrome in rabbits. Infusion of oleic acid (0.1 ml/kg/h, i.v. for 2 h) provoked pulmonary hemorrhage and edema, protein leakage and massive neutrophil infiltration, resulted in severe hypoxemia and impaired lung compliance, accompanying the increase of phospholipase A(2) activity and interleukin-8, and degradation of surfactant in the bronchoalveolar lavage fluid. Infusion of methylprednisolone (60 mg/kg/h, i.v. for 30 min before the oleic acid and then 0.5 mg/kg/h, i.v. for 6 h) did not improve the above described lung injury induced by oleic acid, nor did it suppress phospholipase A(2) activity and degradation of surfactant in bronchoalveolar lavage fluid, while it strongly reduced interleukin-8 levels in both plasma and bronchoalveolar lavage fluid. We conclude that methylprednisolone did not attenuate oleic acid-induced acute lung injury and this can be explained partly by its failure to reduce the increase of phospholipase A(2) activity and the surfactant degradation in the lung, which might also account for its clinical ineffectiveness against early acute respiratory distress syndrome.
Kuwabara
K
K
Discovery Research Laboratories, Division of Pharmacology, Shionogi & Co., Ltd., 3-1-1, Futaba-cho, Toyonaka, Osaka 561-0825, Japan.
Furue
S
S
Tomita
Y
Y
Ueno
M
M
Ono
T
T
Matsukawa
A
A
Yoshinaga
M
M
Mikawa
K
K
Nishina
K
K
Shiga
M
M
Obara
H
H
Hori
Y
Y
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002199:Capillary Permeability / Q000187:drug effects; D015777:Eicosanoids / Q000032:analysis; D016209:Interleukin-8 / Q000097:blood; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D019301:Oleic Acid; D010741:Phospholipases A / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000378:metabolism*; D011817:Rabbits; D012128:Respiratory Distress Syndrome / Q000378:metabolism / Q000517:prevention & control*
D015777:Eicosanoids; D016209:Interleukin-8; D011663:Pulmonary Surfactants; D019301:Oleic Acid; D010741:Phospholipases A; D008775:Methylprednisolone