title: Early treatment of chlorine-induced airway hyperresponsiveness and inflammation with corticosteroids.
abstract: Chlorine (Cl2) is an industrial gas that is highly toxic and irritating when inhaled causing tissue damage and an acute inflammatory response in the airways followed by a long-term airway dysfunction. The aim of this study was to evaluate whether early anti-inflammatory treatment can protect against the delayed symptoms in Cl2-exposed mice. BALB/c mice were exposed by nose-only inhalation using 200ppm Cl2 during 15min. Assessment of airway hyperresponsiveness (AHR), inflammatory cell counts in bronchoalveolar lavage, occurrence of lung edema and lung fibrosis were analyzed 24h or 14days post-exposure. A single dose of the corticosteroid dexamethasone (10 or 100mg/kg) was administered intraperitoneally 1, 3, 6, or 12h following Cl2 exposure. High-dose of dexamethasone reduced the acute inflammation if administered within 6h after exposure but treated animals still displayed a significant lung injury. The effect of dexamethasone administered within 1h was dose-dependent; high-dose significantly reduced acute airway inflammation (100mg/kg) but not treatment with the relatively low-dose (10mg/kg). Both doses reduced AHR 14days later, while lung fibrosis measured as collagen deposition was not significantly reduced. The results point out that the acute inflammation in the lungs due to Cl2 exposure only partly is associated with the long-term AHR. We hypothesize that additional pathogenic mechanisms apart from the inflammatory reactions contribute to the development of long-term airway dysfunction. By using this mouse model, we have validated early administration of corticosteroids in terms of efficacy to prevent acute lung injury and delayed symptoms induced by Cl2 exposure.
authors.affiliation: Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå, Sweden. sofia.jonasson@foi.se
authors.forename: Sofia
authors.initials: S
authors.lastname: Jonasson
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Wigenstam
authors.forename: Bo
authors.initials: B
authors.lastname: Koch
authors.forename: Anders
authors.initials: A
authors.lastname: Bucht
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced* / Q000188:drug therapy*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D002713:Chlorine / Q000633:toxicity*; D003094:Collagen / Q000378:metabolism; D003907:Dexamethasone / Q000627:therapeutic use; D005260:Female; D007249:Inflammation / Q000139:chemically induced* / Q000188:drug therapy*; D019570:Inhalation Exposure; D051379:Mice; D008807:Mice, Inbred BALB C; D011654:Pulmonary Edema / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D015656:Respiratory Mechanics / Q000187:drug effects
chemical_list: D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D002713:Chlorine; D003907:Dexamethasone; D003094:Collagen
keywords: Airway hyperresponsiveness; Chemical-induced lung injury; Chlorine; Corticosteroids; Mouse model; Respiratory mechanics