Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Hill, G.E. et al.

Aprotinin reduces interleukin-8 production and lung neutrophil accumulation after cardiopulmonary bypass.

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.[1]

References

Aprotinin reduces interleukin-8 production and lung neutrophil accumulation after cardiopulmonary bypass. Hill, G.E., Pohorecki, R., Alonso, A., Rennard, S.I., Robbins, R.A. Anesth. Analg. (1996) [Pubmed]

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