Nedocromil sodium and airway inflammation in vivo and in vitro

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Presentation transcript:

Nedocromil sodium and airway inflammation in vivo and in vitro Jagdish L. Devalia, PhD, Csaba Rusznak, MD, Muntasir M. Abdelaziz, MRCP, Robert J. Davies, FRCP Journal of Allergy and Clinical Immunology Volume 98, Issue 5, Pages S51-S57 (November 1996) DOI: 10.1016/S0091-6749(96)70017-9 Copyright © 1996 Mosby, Inc. Terms and Conditions

FIG. 1 Effect of nedocromil sodium 10-3 to 10-7 mol/L on 50 ppb O3-induced release of IL-8 by human bronchial epithelial cells in vitro. Results are expressed as means ± SEM (n = 6 minimum at each time point). *p < 0.05, **p < 0.01 vs nedocromil sodium 0 mol/L. Journal of Allergy and Clinical Immunology 1996 98, S51-S57DOI: (10.1016/S0091-6749(96)70017-9) Copyright © 1996 Mosby, Inc. Terms and Conditions

FIG. 2 Effect of nedocromil sodium 10-5 mol/L on O3-induced synthesis of IL-8, GM-CSF, TNF-α, and sICAM-1 by human bronchial epithelial cells in vitro. Results are expressed as means ± SEM (n = 6 minimum at each time point). *p < 0.05, **p < 0.01, ***p < 0.001 vs 0 ppb O3; #p < 0.05, ##p < 0.01 vs nedocromil sodium 0 mol/L. Journal of Allergy and Clinical Immunology 1996 98, S51-S57DOI: (10.1016/S0091-6749(96)70017-9) Copyright © 1996 Mosby, Inc. Terms and Conditions

FIG. 2 Effect of nedocromil sodium 10-5 mol/L on O3-induced synthesis of IL-8, GM-CSF, TNF-α, and sICAM-1 by human bronchial epithelial cells in vitro. Results are expressed as means ± SEM (n = 6 minimum at each time point). *p < 0.05, **p < 0.01, ***p < 0.001 vs 0 ppb O3; #p < 0.05, ##p < 0.01 vs nedocromil sodium 0 mol/L. Journal of Allergy and Clinical Immunology 1996 98, S51-S57DOI: (10.1016/S0091-6749(96)70017-9) Copyright © 1996 Mosby, Inc. Terms and Conditions

FIG. 2 Effect of nedocromil sodium 10-5 mol/L on O3-induced synthesis of IL-8, GM-CSF, TNF-α, and sICAM-1 by human bronchial epithelial cells in vitro. Results are expressed as means ± SEM (n = 6 minimum at each time point). *p < 0.05, **p < 0.01, ***p < 0.001 vs 0 ppb O3; #p < 0.05, ##p < 0.01 vs nedocromil sodium 0 mol/L. Journal of Allergy and Clinical Immunology 1996 98, S51-S57DOI: (10.1016/S0091-6749(96)70017-9) Copyright © 1996 Mosby, Inc. Terms and Conditions

FIG. 2 Effect of nedocromil sodium 10-5 mol/L on O3-induced synthesis of IL-8, GM-CSF, TNF-α, and sICAM-1 by human bronchial epithelial cells in vitro. Results are expressed as means ± SEM (n = 6 minimum at each time point). *p < 0.05, **p < 0.01, ***p < 0.001 vs 0 ppb O3; #p < 0.05, ##p < 0.01 vs nedocromil sodium 0 mol/L. Journal of Allergy and Clinical Immunology 1996 98, S51-S57DOI: (10.1016/S0091-6749(96)70017-9) Copyright © 1996 Mosby, Inc. Terms and Conditions

FIG. 3 Effect of conditioned medium from human bronchial epithelial cells alone (CM) or with nedocromil sodium 10-5 mol/L (CM+NED) on (A) eosinophil adhesion and (B) eosinophil chemotaxis. *p < 0.05 vs medium 199 (M199). Journal of Allergy and Clinical Immunology 1996 98, S51-S57DOI: (10.1016/S0091-6749(96)70017-9) Copyright © 1996 Mosby, Inc. Terms and Conditions

FIG. 3 Effect of conditioned medium from human bronchial epithelial cells alone (CM) or with nedocromil sodium 10-5 mol/L (CM+NED) on (A) eosinophil adhesion and (B) eosinophil chemotaxis. *p < 0.05 vs medium 199 (M199). Journal of Allergy and Clinical Immunology 1996 98, S51-S57DOI: (10.1016/S0091-6749(96)70017-9) Copyright © 1996 Mosby, Inc. Terms and Conditions

FIG. 4 Release of ECP into culture medium from human airway epithelial cell cultures after 24-hour incubation and exposure to (A) eosinophils (n = 7), (B) eosinophils plus latex beads (n = 9), and (C) eosinophils plus latex beads plus nedocromil sodium 10-5 mol/L (n = 7). *p < 0.05 vs nonactivated eosinophils. Journal of Allergy and Clinical Immunology 1996 98, S51-S57DOI: (10.1016/S0091-6749(96)70017-9) Copyright © 1996 Mosby, Inc. Terms and Conditions

FIG. 5 Mean total eosinophil (EG1) density expressed as cells per square millimeter of bronchial submucosal tissue section, before (biopsy 1, open bars) and after 16 weeks of treatment (biopsy 2, solid bars) with nedocromil sodium (n = 9), albuterol (n = 11), or placebo (n = 12). *p < 0.05, nedocromil sodium–treated group vs albuterol-treated group for difference from pretreatment to posttreatment. Journal of Allergy and Clinical Immunology 1996 98, S51-S57DOI: (10.1016/S0091-6749(96)70017-9) Copyright © 1996 Mosby, Inc. Terms and Conditions

FIG. 6 A, Mean activated eosinophil (EG2) density expressed as cells per square millimeter of bronchial submucosal tissue section, before (biopsy 1, B1) and after 16 weeks of treatment (biopsy 2, B2) with nedocromil sodium (n = 9), albuterol (n = 11), or placebo (n = 12). B, Mean ECP concentration in BAL fluid (nanograms per milliliter) before (lavage 1, L1) and after 16 weeks of treatment (lavage 2, L2). Numbers of paired lavages: nedocromil sodium n = 10; albuterol n = 11, and placebo n = 11. Bars, Mean values. *p < 0.05, nedocromil sodium–treated group vs albuterol-treated group for difference from pretreatment to posttreatment. Journal of Allergy and Clinical Immunology 1996 98, S51-S57DOI: (10.1016/S0091-6749(96)70017-9) Copyright © 1996 Mosby, Inc. Terms and Conditions

FIG. 6 A, Mean activated eosinophil (EG2) density expressed as cells per square millimeter of bronchial submucosal tissue section, before (biopsy 1, B1) and after 16 weeks of treatment (biopsy 2, B2) with nedocromil sodium (n = 9), albuterol (n = 11), or placebo (n = 12). B, Mean ECP concentration in BAL fluid (nanograms per milliliter) before (lavage 1, L1) and after 16 weeks of treatment (lavage 2, L2). Numbers of paired lavages: nedocromil sodium n = 10; albuterol n = 11, and placebo n = 11. Bars, Mean values. *p < 0.05, nedocromil sodium–treated group vs albuterol-treated group for difference from pretreatment to posttreatment. Journal of Allergy and Clinical Immunology 1996 98, S51-S57DOI: (10.1016/S0091-6749(96)70017-9) Copyright © 1996 Mosby, Inc. Terms and Conditions

FIG. 7 Putative mode of action of nedocromil sodium (NS). Journal of Allergy and Clinical Immunology 1996 98, S51-S57DOI: (10.1016/S0091-6749(96)70017-9) Copyright © 1996 Mosby, Inc. Terms and Conditions