Effects of ibuprofen on neutrophil function and acute lung injury in canine endotoxin shock.
The role of the polymorphonuclear leukocyte in the development of acute lung injury has been the subject of much controversy. Experimental lung injury is associated with peripheral leukopenia and the intrapulmonary sequestration of leukocytes. We have previously shown that ibuprofen, a nonsteroidal anti-inflammatory drug, can improve the hemodynamic alterations of canine endotoxin shock. Ibuprofen has also been found to decrease leukocyte adherence. We investigated the dose response of ibuprofen on the increased neutrophil adherence and the extent of lung injury associated with canine endotoxin shock. Single doses of ibuprofen (1, 5, 10, and 20 mg/kg iv) were administered 15 min after Escherichia coli endotoxin. Endotoxemia resulted in leukopenia and an increased neutrophil adherence in both aortic and pulmonary artery blood. Endotoxin-treated animals exhibited increased neutrophils in the bronchoalveolar lavage fluid, a marker of lung injury. The 20-mg/kg ibuprofen dose decreased aortic granulocyte adherence at 30 min, while all ibuprofen doses decreased the aortic adherence at 120 min. The increased pulmonary artery neutrophil adherence was not affected by ibuprofen. Histologically, lung injury was manifested by intravascular leukostasis. Ibuprofen treatment did not affect the histologic or morphometric extent of the lung injury. The leukopenia and increased neutrophil adherence occur rapidly after endotoxemia and are associated with subsequent intravascular sequestration of leukocytes. Agents designed to prevent lung injury must either be given before the insult or be able to block the effects of the toxic products released by the activated granulocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Balk
R A
RA
Department of Medicine, University of Arkansas for Medical Sciences, Little Rock.
Jacobs
R F
RF
Tryka
A F
AF
Townsend
J W
JW
Walls
R C
RC
Bone
R C
RC
D000208:Acute Disease; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000032:analysis; D002448:Cell Adhesion / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D007052:Ibuprofen / Q000494:pharmacology*; D008168:Lung / Q000473:pathology; D008171:Lung Diseases / Q000188:drug therapy* / Q000473:pathology; D009504:Neutrophils / Q000032:analysis / Q000187:drug effects / Q000502:physiology*; D011897:Random Allocation; D012772:Shock, Septic / Q000188:drug therapy* / Q000473:pathology
D007052:Ibuprofen