Treatment with dexamethasone or liposome-encapsuled vitamin E provides beneficial effects after chemical-induced lung injury.
The pathogenesis of lung injury by exposure to highly toxic sulfur and nitrogen mustards involves alkylating damage of the respiratory epithelium followed by an acute inflammatory response and lung edema. The acute phase is followed by long-term respiratory complications characterized by bronchitis, lung fibrosis, and airway hyperreactivity. In this study, we utilized a mouse model for airway inflammation induced by inhalation exposure to the alkylating nitrogen mustard melphalan, in order to investigate possible beneficial treatment effects by the corticosteroid dexamethasone. In addition, we investigated therapeutic efficacy of liposome-encapsuled vitamin E, an antioxidant formulation previously shown to be efficient in counteracting inflammatory conditions. Influx of inflammatory cells to airways, edema formation, and expression of different cytokines were analyzed 6 and 18 hours after exposure to melphalan. In order to evaluate long-term lung effects, we also investigated collagen deposition and accumulation of lymphocytes at 2 and 4 weeks after exposure. A single intraperitoneal injection of dexamethasone (10 mg/kg body weight) 1 hour after melphalan exposure significantly reduced interleukin (IL)-1 and IL-6 in bronchoalveolar lavage fluid (BALF) and diminished the acute airway inflammation. Our results also indicate that early single-dose treatment with dexamethasone protects against long-term effects observed 2-4 weeks after melphalan exposure, as indicated by reduced lymphocytic response in airways and decreased collagen deposition. Furthermore, our results indicate that also vitamin E (50 mg/kg) reduces acute inflammatory cell influx, and suppresses collagen formation in lung tissue, indicating that this drug could be used in combination with corticosteroids for protection against chemical-induced lung injury.
Wigenstam
Elisabeth
E
FOI CBRN Defence and Security, Swedish Defence Research Agency, Umeå, Sweden.
Rocksén
David
D
Ekstrand-Hammarström
Barbro
B
Bucht
Anders
A
D000210:Acute-Phase Reaction / Q000517:prevention & control; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002057:Burns, Chemical / Q000188:drug therapy*; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D003907:Dexamethasone / Q000627:therapeutic use*; D004337:Drug Carriers; D005260:Female; D008081:Liposomes; D055370:Lung Injury / Q000188:drug therapy* / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000187:drug effects; D011654:Pulmonary Edema / Q000473:pathology / Q000517:prevention & control; D011658:Pulmonary Fibrosis / Q000473:pathology / Q000517:prevention & control; D014810:Vitamin E / Q000008:administration & dosage / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016207:Cytokines; D004337:Drug Carriers; D008081:Liposomes; D014810:Vitamin E; D003907:Dexamethasone; D003094:Collagen