Corticosteroid treatment inhibits airway hyperreactivity and lung injury in a murine model of chemical-induced airway inflammation
(English)Manuscript (preprint) (Other academic)
Context: Exposure to toxic alkylating mustard agents causes both acute and long-term effects to the lungs as indicated by increased number of inflammatory cells in airways, lung edema and lung tissue fibrosis. We have previously demonstrated that treatment with the corticosteroid dexamethasone 1 hr after lung exposure to the alkylating mustard melphalan, protect mice from acute and sub-acute inflammatory responses, as well as from lung fibrosis.
Objective: In order to address the importance of early anti-inflammatory treatment, we investigated the therapeutic effect of dexamethasone administered 1, 2 or 6 hrs following exposure to melphalan.
Methods: Female C57BL/6 mice were via intratracheal instillation exposed to the nitrogen mustard analogue melphalan and treated i.p. with dexamethasone 1, 2 or 6 hours after exposure. Twenty hours or 14 days post exposure mice were subjected to analysis of respiratory mechanics where the effects of incremental doses of methacholine on central and peripheral lung components were measured. We also determined the amount of neutrophils and lymphocytes in the bronchoalveolar lavage fluid and measured the amount of collagen content in the lungs.
Results: Melphalan exposure exerted a significant effect on both central and peripheral respiratory function. Dexamethasone given one hour post exposure protected the lung against the damaging effects of melphalan. Collagen deposition 14 days after exposure was decreased with dexamethasone treatment.
Conclusion: Early dexamethasone treatment (within one hour after exposure) is important in order to reduce the airway reactivity and inflammation caused by toxic alkylating mustards such as melphalan.
alkylating nitrogen mustard, chemical-induced lung injury, corticosteroids, respiratory mechanics, mouse models
Medical and Health Sciences
Research subject Lung Medicine
IdentifiersURN: urn:nbn:se:umu:diva-52717OAI: oai:DiVA.org:umu-52717DiVA: diva2:506853