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Author Wigenstam, Elisabeth ♦ Elfsmark, Linda ♦ Koch, Bo
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ ANIMAL TISSUES ♦ CHLORINE ♦ COLLAGEN ♦ DEXAMETHASONE ♦ EDEMA ♦ EOSINOPHILS ♦ FIBROSIS ♦ HEART ♦ INFLAMMATION ♦ INHALATION ♦ INJURIES ♦ LUNGS ♦ LYMPHOKINES ♦ MACROPHAGES ♦ NEUTROPHILS ♦ PATHOGENESIS ♦ RATS ♦ REPAIR
Abstract We investigated acute and delayed respiratory changes after inhalation exposure to chlorine (Cl{sub 2}) with the aim to understand the pathogenesis of the long-term sequelae of Cl{sub 2}-induced lung-injury. In a rat model of nose-only exposure we analyzed changes in airway hyperresponsiveness (AHR), inflammatory responses in airways, expression of pro-inflammatory markers and development of lung fibrosis during a time-course from 5 h up to 90 days after a single inhalation of Cl{sub 2}. A single dose of dexamethasone (10 mg/kg) was administered 1 h following Cl{sub 2}-exposure. A 15-min inhalation of 200 ppm Cl{sub 2} was non-lethal in Sprague-Dawley rats. At 24 h post exposure, Cl{sub 2}-exposed rats displayed elevated numbers of leukocytes with an increase of neutrophils and eosinophils in bronchoalveolar lavage (BAL) and edema was shown both in lung tissue and the heart. At 24 h, the inflammasome-associated cytokines IL-1β and IL-18 were detected in BAL. Concomitant with the acute inflammation a significant AHR was detected. At the later time-points, a delayed inflammatory response was observed together with signs of lung fibrosis as indicated by increased pulmonary macrophages, elevated TGF-β expression in BAL and collagen deposition around airways. Dexamethasone reduced the numbers of neutrophils in BAL at 24 h but did not influence the AHR. Inhalation of Cl{sub 2} in rats leads to acute respiratory and cardiac changes as well as pulmonary inflammation involving induction of TGF-β1. The acute inflammatory response was followed by sustained macrophage response and lack of tissue repair. It was also found that pathways apart from the acute inflammatory response contribute to the Cl{sub 2}-induced respiratory dysfunction. - Highlights: • Inhalation of Cl{sub 2} leads to acute lung inflammation and airway hyperreactivity. • Cl{sub 2} activates an inflammasome pathway of TGF-β induction. • Cl{sub 2} leads to a fibrotic respiratory disease. • Treatment with corticosteroids alone is insufficient to counteract acute lung injury.
ISSN 0041008X
Educational Use Research
Learning Resource Type Article
Publisher Date 2016-10-15
Publisher Place United States
Journal Toxicology and Applied Pharmacology
Volume Number 309


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