Application of Naltrexone and Nalmefene for alleviation of airway inflammation in OVA-induced murine model of asthma
Date Issued
2009
Date
2009
Author(s)
Wang, Yu-Cheng
Abstract
Asthma is one of the most common airway inflammatory disease in the industrialized society and is the prevalence is very high in developed and developing countries. It might be caused by many factors including genetic factors, environmental factors and life style. The immune mechanism of asthma is that T helper cells are abnormally differentiated to Th2 immune response. The symptoms of asthma are intermittent and reversible airway obstruction leading to recurrent episodes of wheezing, breathlessness, chest tightness, and cough; bronchial hyperresponsiveness (BHR), which is defined as an increased sensitivity to bronchoconstrictors such as histamine or cholinergic agonists; and airway inflammation. Many researches have indicated that opioid receptors are found on immune cells, and participate in regulation of immune response. Naltrexone and nalmefene are antagonists of opioid receptors, and they can suppress inflammation with blocking the opioid receptors. For this reason, the aim of this study is to find out if naltrexone and nalmefene could suppress airway inflammation in OVA-induced murine model of asthma. The secretion of IL-6, IL-12, IL-10 and TNF-α of dentritic cells and macrophages stimulated with LPS were decreased by treatment with naltrexone and nalmefene. These results showed that naltrexone and nalmefene can reduce the secretion of cytokines related with inflammation. Further, in the OVA-induced murine model of asthma, analyzing the AHR, lung fuction, cytokines and chemokines which is related to inflammation suggesting that naltrexone and nalmefene can suppress the AHR and eosinophils assembling, and reduce the production of cytokines and chemokines connected with inflammation such as eotaxin, IL-6 and TNF-α in BALF. However, naltrexone and nalmefene can not affect the levels of antigen-specific antibodies in serum and the production of IL-5 in BALF, and have no effect in the levels of IL-5, IL-10 and IL-12 produced by splenocytes. Therefore, the results of study suggest that naltrexone and nalmefene can suppress the inflammation by blocking the opioid receptor, and reduce the airway inflammation in asthma, but have no effect to change the immune response. Finally, the mechanisms are not clear, so it needs futher investigation further in the future.
Subjects
asthma
anti-inflammation
opioid receptor
naltrexone
nalmefene
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