Effects of nebulised magnesium sulphate on inflammation and function of the guinea-pig airway

Turner, Dawn L., Ford, William R. ORCID: https://orcid.org/0000-0002-8792-6169, Kidd, Emma J. ORCID: https://orcid.org/0000-0001-5507-1170, Broadley, Kenneth J. ORCID: https://orcid.org/0000-0002-3339-2050 and Powell, Colin 2017. Effects of nebulised magnesium sulphate on inflammation and function of the guinea-pig airway. European Journal of Pharmacology 801 , pp. 79-85. 10.1016/j.ejphar.2017.03.004

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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 24 h after OVA exposure. Airway hyperresponsiveness to inhaled histamine and inflammatory cells in bronchoalveolar lavage fluid were recorded 24 h 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Subjects:	R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords:	Magnesium sulphate; Asthma; Bronchoprotection; Guinea-pigs; Airways inflammation; Lipopolysaccharide
Additional Information:	Released with a Creative Commons Attribution Non-Commercial No Derivatives License (CC BY-NC-ND)
Publisher:	Elsevier
ISSN:	0014-2999
Date of First Compliant Deposit:	20 March 2017
Date of Acceptance:	7 March 2017
Last Modified:	26 Nov 2024 00:00
URI:	https://orca.cardiff.ac.uk/id/eprint/99174

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