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.