APROTININ REDUCES INTERLEUKIN-8 PRODUCTION AND LUNG NEUTROPHIL ACCUMULATION AFTER CARDIOPULMONARY BYPASS

Pulmonary neutrophil entrapment and resultant oxidative injury is thou ght to be the primary mechanism of cardiopulmonary bypass (CPB) induce d lung injury. Interleukin-8 (IL-8), a potent neutrophil chemoattracta nt induced by cytokines, including tumor necrosis factor-alpha (TNF), is found in increased concentrations in bronchial alveolar lavage flui d (BALF) in lung inflammation. Since aprotinin reduces TNF release dur ing CPB, the effects of aprotinin on BALF IL-8 concentrations and neut rophil levels were determined after CPB in adult humans. Study patient s were equally divided into a control group (n = 8, Group 1) and an ap rotinin-treated group (n = 8, Group 2). ill vitro neutrophil chemotaxi s was done with volunteer neutrophils using three different chemoattra ctants: 1) N-formyl-1-methionyl-1-leucyl-1-phenylalanine (FMLP); 2) th e supernatant of a human bronchial epithelial cell culture line, A549, after 24 h of TNF stimulation with or without aprotinin or N-alpha-to syl-L-lysine chloromethyl ketone (TLCK) (a potent protease inhibitor), and 3) BALF. Aprotinin treatment significantly (P < 0.05) reduced pos t-CPB BALF IL-8 concentrations and percentage of neutrophils. In vitro , BALF from Group 1 had significantly greater chemotactic ability when compared with Group 2. The TNF stimulated A549 cell culture supernata nt had significantly (P < 0.05) greater chemotactic ability than contr ol supernatant, while aprotinin and TLCK significantly (P < 0.05) redu ced this chemotactic ability. These results demonstrate that aprotinin blunts IL-8 production and reduces neutrophil lung accumulation post- CPB.