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[Inhibitory effect of chloroquine on airway hyperresponsiveness in asthmatic mice]

Xiao-Chun Sun¹, Xiao-Yan Hu, Li-Jia Wang

¹Department of Respiratory Medicine, Children's Hospital Affiliated to Chongqing Medical University, Chongqing 400014, China.E-mail: 1103751123@qq.com.

Nan Fang Yi Ke Da Xue Xue Bao = Journal of Southern Medical University

|January 24, 2015

Abstract

Objective:

To investigate the effect of chloroquine on airway hyperresponsiveness in asthmatic mice and explore the possible mechanism.

Methods:

Balb/c mouse models of asthma established using OVA received intraperitoneal injections of chloroquine, dexamethasone, or both prior to OVA challenge. Within 24 h after the final challenge, airway hyper- responsiveness (AHR) of the mice was assessed, and the total cell count and the counts of different cell populations in the bronchoalveolar lavage fluid (BALF) were determined under light microscopy. The severity of lung inflammation was evaluated using HE staining, and the concentrations of IL-6 and PGF2α in the BALF were detected by enzyme-linked immunosorbent assay (ELISA).

Results:

Chloroquine pretreatment significantly decreased AHR (P<0.001) in the asthmatic mice and reduced the total cell count (P<0.01), eosinophils (P<0.001), neutrophils (P<0.01), and PGF2α levels in the BALF. Chloroquine combined with low-dose dexamethasone significantly lessened inflammations around the bronchioles (P<0.05) and blood vessels (P<0.01) in the lung tissue, and obviously lowered IL-6 (P<0.05) and PGF2α (P<0.001) in the BALF in the asthmatic mice.

Conclusion:

Chloroquine can inhibit AHR in asthmatic mice and produce better anti-inflammatory effect when combined with dexamethasone for treatment of neutrophilic asthma.

Insights

Chloroquine effectively reduced airway hyperresponsiveness and inflammation in asthmatic mice. Combining chloroquine with dexamethasone enhanced these anti-inflammatory effects, particularly in neutrophilic asthma.

Area of Science:

Immunology
Pharmacology
Respiratory Medicine

Background:

Asthma is a chronic respiratory disease characterized by airway hyperresponsiveness (AHR) and inflammation.
Current treatments aim to manage symptoms and reduce exacerbations, but novel therapeutic strategies are continuously sought.

Purpose of the Study:

To evaluate the efficacy of chloroquine in mitigating AHR in a mouse model of asthma.
To investigate the underlying anti-inflammatory mechanisms of chloroquine and its potential synergistic effects with dexamethasone.

Main Methods:

Asthma was induced in Balb/c mice using ovalbumin (OVA) sensitization and challenge.
Mice received intraperitoneal injections of chloroquine, dexamethasone, or a combination prior to OVA challenge.
Airway hyperresponsiveness, bronchoalveolar lavage fluid (BALF) cell counts, lung inflammation (HE staining), and BALF cytokine levels (IL-6, PGF2α) were assessed.

Main Results:

Chloroquine significantly reduced AHR, total cell counts, eosinophils, neutrophils, and prostaglandin F2α (PGF2α) levels in BALF.
Combination therapy with chloroquine and low-dose dexamethasone further attenuated lung inflammation and lowered IL-6 and PGF2α concentrations in BALF.

Conclusions:

Chloroquine demonstrates significant potential in inhibiting AHR and reducing inflammation in asthmatic mice.
Combination therapy with dexamethasone offers enhanced anti-inflammatory benefits, suggesting a promising therapeutic approach for neutrophilic asthma.

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