Aprotinin Reduces Interleukin-8 Production and Lung Neutrophil Accumulation After Cardiopulmonary Bypass

Publisher Website
Google Scholar
Abstract
Pulmonary neutrophil entrapment and resultant oxida- tive injury is thought to be the primary mechanism of cardiopulmonary bypass (CPB) induced lung injury. Interleukin-8 (IL-@, a potent neutrophil chemoattrac- tant induced by cytokines, including tumor necrosis factor-a (TNF), is found in increased concentrations in bronchial alveolar lavage fluid (BALF) in lung inflam- mation. Since aprotinin reduces TNF release during CPB, the effects of aprotinin on BALF IL-S concentra- tions and neutrophil levels were determined after CPB in adult humans. Study patients were equally divided into a control group (n = 8, Group 1) and an aprotinin- treated group (n = 8, Group 2). In vitro neutrophil chemotaxis was done with volunteer neutrophils using three different chemoattractants: 1) N-formyl-l- methionyl-1-leucyl-1-phenylalanine (FMLP); 2) the supernatant of a human bronchial epithelial cell culture line, A.549, after 24 h of TNF stimulation with or without aprotinin or N-a-tosyl-L-lysine chloromethyl ketone (TLCK) (a potent protease inhibitor), and 3) BALF. Aprotinin treatment significantly (P < 0.05) reduced post-CPB BALF IL-8 concentrations and percentage of neutrophils. In vitro, BALF from Group 1 had signifi- cantly greater chemotactic ability when compared with Group 2. The TNF stimulated A549 cell culture super- natant had significantly (P < 0.05) greater chemotactic ability than control supernatant, while aprotinin and TLCK significantly (P < 0.05) reduced this chemotactic ability. These results demonstrate that aprotinin blunts IL-8 production and reduces neutrophil lung accumu- lation post-CPB. (Anesth Analg 1996;83:696-700)

This publication has 14 references indexed in Scilit: