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dc.contributor.authorReeves, Emer P
dc.contributor.authorWilliamson, Michael
dc.contributor.authorO'Neill, Shane J
dc.contributor.authorGreally, Peter
dc.contributor.authorMcElvaney, Noel G
dc.date.accessioned2012-02-01T10:00:38Z
dc.date.available2012-02-01T10:00:38Z
dc.date.issued2012-02-01T10:00:38Z
dc.identifier.citationAm J Respir Crit Care Med. 2011 Jun 1;183(11):1517-23. Epub 2011 Feb 17.en_GB
dc.identifier.issn1535-4970 (Electronic)en_GB
dc.identifier.issn1073-449X (Linking)en_GB
dc.identifier.pmid21330456en_GB
dc.identifier.doi10.1164/rccm.201101-0072OCen_GB
dc.identifier.urihttp://hdl.handle.net/10147/207157
dc.description.abstractRATIONALE: Inflammation within the cystic fibrosis (CF) lung is mediated by inflammatory chemokines, such as IL-8. IL-8 is protected from proteolytic degradation in the airways by binding to glycosaminoglycans, while remaining active. Evidence that increased hypertonicity of airway secretions induced by hypertonic saline treatment alters levels of IL-8 is lacking. OBJECTIVES: To investigate the antiinflammatory effect of hypertonic saline (HTS) treatment within the CF lung by focusing on IL-8. METHODS: Degradation of IL-8 in CF lung secretions after treatment with glycosaminoglycan lyases and HTS was analyzed by Western blot analysis and ELISA. The ex vivo chemotactic activity of purified neutrophils in response to CF airway secretions was evaluated post nebulization of HTS (7% saline). MEASUREMENTS AND MAIN RESULTS: In vivo CF bronchoalveolar lavage fluid (BALF) IL-8 levels were significantly higher than the control group (P < 0.05). Digesting glycosaminoglycans in CF BALF displaced IL-8 from glycosaminoglycan matrices, rendering the chemokine susceptible to proteolytic cleavage. High sodium concentrations also liberate IL-8 in CF BALF in vitro, and in vivo in CF sputum from patients receiving aerosolized HTS, resulting in degradation of IL-8 and decreased neutrophil chemotactic efficiency. CONCLUSIONS: Glycosaminoglycans possess the ability to influence the chemokine profile of the CF lung by binding and stabilizing IL-8, which promotes neutrophil chemotaxis and activation. Nebulized hypertonic saline treatment disrupts the interaction between glycosaminoglycans and IL-8, rendering IL-8 susceptible to proteolytic degradation with subsequent decrease in neutrophil chemotaxis, thereby facilitating resolution of inflammation.
dc.language.isoengen_GB
dc.subject.meshAdministration, Inhalationen_GB
dc.subject.meshAdulten_GB
dc.subject.meshBlotting, Westernen_GB
dc.subject.meshBronchoalveolar Lavage Fluid/immunologyen_GB
dc.subject.meshCystic Fibrosis/complications/*drug therapy/immunologyen_GB
dc.subject.meshElectrophoresis, Polyacrylamide Gelen_GB
dc.subject.meshEnzyme-Linked Immunosorbent Assayen_GB
dc.subject.meshGlycosaminoglycans/immunologyen_GB
dc.subject.meshHumansen_GB
dc.subject.meshInflammation/complications/drug therapy/immunologyen_GB
dc.subject.meshInterleukin-8/*drug effects/immunologyen_GB
dc.subject.meshMiddle Ageden_GB
dc.subject.meshNebulizers and Vaporizersen_GB
dc.subject.meshSaline Solution, Hypertonic/*administration & dosageen_GB
dc.subject.meshSputum/drug effects/*immunologyen_GB
dc.subject.meshYoung Adulten_GB
dc.titleNebulized hypertonic saline decreases IL-8 in sputum of patients with cystic fibrosis.en_GB
dc.contributor.departmentRespiratory Research Division, Department of Medicine, Royal College of Surgeons , in Ireland, Beaumont Hospital, Dublin 9, Ireland. emerreeves@rcsi.ieen_GB
dc.identifier.journalAmerican journal of respiratory and critical care medicineen_GB
dc.description.provinceLeinster
html.description.abstractRATIONALE: Inflammation within the cystic fibrosis (CF) lung is mediated by inflammatory chemokines, such as IL-8. IL-8 is protected from proteolytic degradation in the airways by binding to glycosaminoglycans, while remaining active. Evidence that increased hypertonicity of airway secretions induced by hypertonic saline treatment alters levels of IL-8 is lacking. OBJECTIVES: To investigate the antiinflammatory effect of hypertonic saline (HTS) treatment within the CF lung by focusing on IL-8. METHODS: Degradation of IL-8 in CF lung secretions after treatment with glycosaminoglycan lyases and HTS was analyzed by Western blot analysis and ELISA. The ex vivo chemotactic activity of purified neutrophils in response to CF airway secretions was evaluated post nebulization of HTS (7% saline). MEASUREMENTS AND MAIN RESULTS: In vivo CF bronchoalveolar lavage fluid (BALF) IL-8 levels were significantly higher than the control group (P < 0.05). Digesting glycosaminoglycans in CF BALF displaced IL-8 from glycosaminoglycan matrices, rendering the chemokine susceptible to proteolytic cleavage. High sodium concentrations also liberate IL-8 in CF BALF in vitro, and in vivo in CF sputum from patients receiving aerosolized HTS, resulting in degradation of IL-8 and decreased neutrophil chemotactic efficiency. CONCLUSIONS: Glycosaminoglycans possess the ability to influence the chemokine profile of the CF lung by binding and stabilizing IL-8, which promotes neutrophil chemotaxis and activation. Nebulized hypertonic saline treatment disrupts the interaction between glycosaminoglycans and IL-8, rendering IL-8 susceptible to proteolytic degradation with subsequent decrease in neutrophil chemotaxis, thereby facilitating resolution of inflammation.


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