Aerosol administration of dexamethasone and methotrexate attenuated Th2 reaction and eosinophil infiltration of the lung in ovalbumin sensitized mice

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Aerosol administration of dexamethasone and methotrexate attenuated Th2 reaction and eosinophil infiltration of the lung in ovalbumin sensitized mice

Objective To elucidate the mechanism of anti-inflammatory effect of dexamethasone and methotrexate on pulmonary Th2 reaction and eosinophil infiltration in ovalbumin sensitized mice, and search for the possibility of aerosol administration of other anti-inflammatory drugs in the management of asthma except for glucocorticoids.Methods Sixty C57b1/6 mice were sensitized and challenged with ovalbumin, aerosol dexamethasone and methotrexate were administered after challenge. Mice lung were fixed in paraformaldehyde and IL-4, IL-5 expression was detected by immunocytochemistry-in situ hybridization. Lung slides were also stained with eosin and hematoxylin, and pathological changes were observed.Results Ovalbumin aerosol inhalation caused a mixed inflammatory infiltration dominated by CD4+ T lymphocytes and eosinophils in the lung of sensitized mice. 85.2%-88.2% and 81.4%-91.8% of the CD4+ T lymphocytes were IL-4 mRNA+ or IL-5 mRNA+ respectively, and few CD8+ T lymphocytes were IL-4 or IL-5 positive (<2%). 78.8%-80.8% of IL-4 mRNA+ cells and 78.0%-86.8%of IL-5 mRNA+ cells were CD4+ T lymphocytes. Aerosol administration of dexamethasone and methotrexate after challenge inhibited IL-4 and IL-5 expression, and lung eosinophil infiltration were attenuated. And dexamethasone was more effective. These two drugs had no effect on the ratio of IL-4 or IL-5 expression of CD4+ T lymphocytes, and the percentages of CD4+ T lymphocytes of the IL-4 mRNA+ or IL-5 mRNA+ cells were not affected. The anti-inflammatory effect was non-specific. In addition, aerosol administration of dexamethasone enhanced IL-4 expression and methotrexate promoted eosinophil infiltration 12 h after challenge.Conclusion Aerosol administration of dexamethasone and methotrexate attenuated pulmonary Th2 reaction in ovalbumin sensitized mice. Aerosol administration of drug exerts its effect at the site of inflammation, which is more effective with less side effects. But at the beginning, aerosol administration might promote inflammation. In this way, oral or intravenous injection of glucocorticoids should be given to moderate to severe asthmatic patients, and aerosol gulcocorticoids should be adminstered after the disease was under control. Methotrexate was less effective than dexamethasone but more irritative, and should not be given by inhalation, Intravenous injection of methotrexate should be administrated to asthmatic patients who respond poorly to glucocorticoids as an auxiliary therapeutic measure.