title: Effects of nebulised magnesium sulphate on inflammation and function of the guinea-pig airway.
abstract: Magnesium sulphate is a potential treatment for acute severe asthma. However, the mechanisms and dose-response relationships are poorly understood. The first objective of this study was to examine whether inhaled magnesium sulphate exerts bronchodilator activity measured as bronchoprotection against histamine-induced bronchoconstriction in conscious guinea-pigs alone and combined with salbutamol. Secondly, we examined whether inhaled magnesium sulphate inhibits airways inflammation and function in models of neutrophilic and eosinophilic lung inflammation induced, respectively, by inhaled lipopolysaccharide or the inhaled antigen, ovalbumin (OVA). Airway function was measured in conscious guinea-pigs as specific airway conductance (sGaw) by whole-body plethysmography. Anti-inflammatory activity was measured against lung inflammatory cell influx induced by OVA inhalation in OVA-sensitised animals or by lipopolysaccharide (LPS) exposure of non-sensitised animals. Airway function (sGaw) was measured over 24h after OVA exposure. Airway hyperresponsiveness to inhaled histamine and inflammatory cells in bronchoalveolar lavage fluid were recorded 24h after OVA or LPS challenge. Histamine-induced bronchoconstriction was inhibited by inhaled magnesium sulphate or salbutamol alone and in combination, they produced synergistic bronchoprotection. LPS-induced neutrophil influx was inhibited by 6 days pretreatment with magnesium sulphate. Early and late asthmatic responses in OVA sensitised and challenged animals were attenuated by magnesium sulphate. Lung inflammatory cells were increased by OVA, macrophages being significantly reduced by magnesium sulphate. Nebulised magnesium sulphate protects against histamine-induced bronchoconstriction in conscious guinea-pigs and exerts anti-inflammatory activity against pulmonary inflammation induced by allergen (OVA) or LPS. These properties of magnesium sulphate explain its beneficial actions in acute asthma.
authors.affiliation: Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, Cathays Park, Cardiff CF10 3NB, Wales, UK.
authors.forename: Dawn L
authors.initials: DL
authors.lastname: Turner
authors.affiliation: Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, Cathays Park, Cardiff CF10 3NB, Wales, UK.
authors.forename: William R
authors.initials: WR
authors.lastname: Ford
authors.affiliation: Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, Cathays Park, Cardiff CF10 3NB, Wales, UK.
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Kidd
authors.affiliation: Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, Cathays Park, Cardiff CF10 3NB, Wales, UK. Electronic address: BroadleyKJ@Cardiff.ac.uk.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Broadley
authors.affiliation: Department of Child Health, Children's Hospital for Wales, Institute of Molecular and Experimental Medicine, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XW, Wales, UK.
authors.forename: Colin
authors.initials: C
authors.lastname: Powell
mesh_terms: D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D004347:Drug Interactions; D004804:Eosinophils / Q000187:drug effects; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D008278:Magnesium Sulfate / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009330:Nebulizers and Vaporizers; D009504:Neutrophils / Q000187:drug effects; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology
chemical_list: D001993:Bronchodilator Agents; D008278:Magnesium Sulfate; D006632:Histamine; D010047:Ovalbumin; D000420:Albuterol
keywords: Airways inflammation; Asthma; Bronchoprotection; Guinea-pigs; Lipopolysaccharide; Magnesium sulphate