Acute respiratory changes and pulmonary inflammation involving a pathway of TGF-beta 1 induction in a rat model of chlorine-induced lung injury

• We investigated acute and delayed respiratory changes after inhalation exposure to chlorine (Cl-2) with the aim to understand the pathogenesis of the long-term sequelae of Cl-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-2. A single dose of dexamethasone (10 mg/Kg) was administered 1 h following Cl-2-exposure. A 15-min inhalation of 200 ppm Cl-2 was non-lethal in Sprague-Dawley rats. At 24 h post exposure, Cl-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-1 beta 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-beta 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-2 in rats leads to acute respiratory and cardiac changes as well as pulmonary inflammation involving induction of TGF-beta 1. 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(2-)induced respiratory dysfunction. 

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)

Nyckelord

Chlorine

Chemical-induced lung injury

Airway hyperresponsiveness

Respiratory mechanics

flammation

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)