Montelukast reduces inhaled chlorine triggered airway hyperresponsiveness and airway inflammation in the mouse
Bibliographic record
Abstract
Background and Purpose Cysteinyl leukotrienes (CysLTs) are pro‐inflammatory lipid mediators that exacerbate disease state in several asthma phenotypes including asthma induced by allergen, virus and exercise. However, the role of CysLTs in irritant‐induced airway disease is not well characterized. The purpose of the current study was to investigate the effect of montelukast, a CysLT 1 receptor antagonist, on parameters of irritant‐induced asthma induced by inhalation of chlorine in the mouse. Experimental Approach BALB/c mice were exposed to chlorine in air (100 ppm, for 5 min). Montelukast (3 mg·kg −1 ) or the vehicle (1% methylcellulose) was administered 24 and 1 h prior to chlorine exposure and 1 h prior to outcome measurements. Twenty‐four hours after exposure, responses to inhaled aerosolized methacholine, cell composition and an array of cytokines/chemokines in bronchoalveolar lavage (BAL) fluid were measured. Neutralizing antibodies against IL‐6 and VEGF were administered prior to exposures. Key Results Montelukast reduced chlorine ‐induced airway hyperresponsiveness (AHR) to methacholine in the peripheral lung compartment as estimated from dynamic elastance, but not in large conducting airways. Montelukast treatment attenuated chlorine‐induced macrophage influx, neutrophilia and eosinophilia in BAL fluid. Chlorine exposure increased VEGF, IL‐6, the chemokines KC and CCL3 in BAL fluid. Montelukast treatment prevented chlorine‐induced increases in VEGF and IL‐6. Anti‐IL‐6 antibody inhibited chlorine‐induced neutrophilia and reduced AHR. Conclusions and Implications Pre‐treatment with montelukast attenuated chlorine‐induced neutrophilia and AHR in mice. These effects are mediated, in part, via IL‐6.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".