title: Aprotinin reduces interleukin-8 production and lung neutrophil accumulation after cardiopulmonary bypass.
abstract: Pulmonary neutrophil entrapment and resultant oxidative injury is thought to be the primary mechanism of cardiopulmonary bypass (CPB) induced lung injury. Interleukin-8 (IL-8), a potent neutrophil chemoattractant induced by cytokines, including tumor necrosis factor-alpha (TNF), is found in increased concentrations in bronchial alveolar lavage fluid (BALF) in lung inflammation. Since aprotinin reduces TNF release during CPB, the effects of aprotinin on BALF IL-8 concentrations 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 aprotin-intreated group (n = 8, Group 2). In vitro neutrophil chemotaxis was done with volunteer neutrophils using three different chemoattractants: 1) N-formyl-1-methionyl-1-leucyl-1-phenylalanine (FMLP); 2) the supernatant of a human bronchial epithelial cell culture line, A549, after 24 h of TNF stimulation with or without aprotinin or N-alpha-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 significantly greater chemotactic ability when compared with Group 2. The TNF stimulated A549 cell culture supernatant 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 accumulation post-CPB.
authors.affiliation: Department of Internal Medicine, University of Nebraska Medical Center, Omaha 68198-4455, USA.
authors.forename: G E
authors.initials: GE
authors.lastname: Hill
authors.forename: R
authors.initials: R
authors.lastname: Pohorecki
authors.forename: A
authors.initials: A
authors.lastname: Alonso
authors.forename: S I
authors.initials: SI
authors.lastname: Rennard
authors.forename: R A
authors.initials: RA
authors.lastname: Robbins
mesh_terms: D000328:Adult; D000368:Aged; D007611:Aprotinin / Q000627:therapeutic use*; D001980:Bronchi / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D018929:Cell Culture Techniques; D002630:Chemotactic Factors / Q000037:antagonists & inhibitors; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D017077:Culture Media, Conditioned; D006490:Hemostatics / Q000627:therapeutic use*; D006801:Humans; D016209:Interleukin-8 / Q000032:analysis / Q000037:antagonists & inhibitors*; D007958:Leukocyte Count / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000473:pathology; D011014:Pneumonia / Q000276:immunology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D014107:Tosyllysine Chloromethyl Ketone / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology
chemical_list: D002630:Chemotactic Factors; D017077:Culture Media, Conditioned; D006490:Hemostatics; D016209:Interleukin-8; D011500:Protein Synthesis Inhibitors; D014409:Tumor Necrosis Factor-alpha; D014107:Tosyllysine Chloromethyl Ketone; D009240:N-Formylmethionine Leucyl-Phenylalanine; D007611:Aprotinin