Reduction of Airway Hyperresponsiveness by KWLL inDermatophagoides-pteronyssinus-Challenged Mice

Chih-Che Lin,Chung-Jen Chiang,Chin-Jen Wu,Yun-Peng Chao,Shulhn-Der Wang,Li-Jen Lin,Shung-Te Kao,Hong-Jye Hong

doi:10.1155/2013/262391

Abstract

Urine therapy has been commonly practiced in ancient civilizations including those of India, China, and Greece. The traditional Chinese medicine KWLL, the precipitation of human urine, has been used in China to alleviate the symptoms of asthma for thousands of years. However, the mechanism of action by which KWLL exerts its immunotherapy is unclear. This study attempted to elucidate the pharmacology of KWLL in mice that had been challenged recurrently by Dermatophagoides pteronyssinus (Der p). BALB/c mice were orally administered KWLL (1 g/kg) before an intratracheal (i.t.) challenge of Der p. Allergic airway inflammation and remodeling were provoked by repetitive Der p (50 μg/mice) challenges six times at 1 wk intervals. Airway hypersensitivity, histological lung characteristics, and the expression profiles of cytokines and various genes were assessed. KWLL reduced Der p-induced airway hyperresponsiveness and inhibited eosinophil infiltration by downregulating the protein expression of IL-5 in bronchoalveolar lavage fluid (BALF). It also inhibited neutrophil recruitment by downregulating IL-17A in BALF. KWLL effectively diminished inflammatory cells, goblet cell hyperplasia, and mRNA expression of IL-6 and IL-17A in the lung. The reduction by KWLL of airway inflammatory and hyperresponsiveness in allergic asthmatic mice was mediated via immunomodulation of IL-5, IL-6, and IL-17A.

Highlights

The incidence of asthma has increased dramatically, along with its morbidity and mortality
We used a repetitive Dermatophagoides pteronyssinus (Der p) challenge mouse model to investigate the impact of oral KWLL on allergen-induced airway hyperresponsiveness
We found that the mice in the Der p group had higher Penh values than the PBS group, a difference that was statistically significant at the maximum dose of methacholine

Summary

Introduction

The incidence of asthma has increased dramatically, along with its morbidity and mortality. It is a common chronic disorder in the world, especially in developed countries, and 255,000 people died of asthma in 2005 [1, 2]. The prevalence of asthma has increased approximately 3-fold in children over the past few decades, and 300 million people are affected worldwide [3]. The diagnosis and management of asthma are more difficult than other chronic diseases because asthma patients have complex heterogeneous syndromes and pharmacological responses to medicine [4]. Most patients with asthma use a combination of steroids and β2-adrenergic agonists as the standard therapy [5, 6]. Patients who inhaled these drugs over the long term can develop serious side effects, and some patients do not satisfactorily respond to these drugs [7]

Methods

Results

Conclusion