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 antiinflammatory effect of dex amethasone and methotrexate on pulmonary Th2 reaction aid eosinophil i nfiltration in ovalbumin sensitized mice, and search for the possibili ty of aerosol administration of other anti-inflammatory drugs in the m anagement of asthma except for glucocorticoids. Methods Sixty C57b1/6 mice were sensitized and challenged with ovalbumin, aerosol dexamethas one and methotrexate were administered after challenge. Mice lung were fixed in paraformaldehyde and IL-4, IL-5 expression was detected by i mmunocytochemistry-situ hybridization. Lung slides were also stained w ith eosin and hematoxylin, and pathological changes were observed. Res ults Ovalbumin aerosol inhalation caused a mixed inflammatory infiltra tion dominated by CD4 + T lymphocytes and eosinophils in the lung of s ensitized 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 lymphoc ytes were IL-4 or IL-5 positive (<2%). 78.8%-80.8% of IL-4 mRNA + cell s and 78.0%-86.8% of IL-5 mRNA + cells were CD4 + T lymphocytes. Aeros ol administration of dexamethasone and methotrexate after challenge in hibited IL-4 and IL-5 expression, and lung eosinophil infiltration wer e attenuated. And dexamethasone was more effective. These two drugs ha d no effect on the ratio of IL-4 or IL-5 expression of CD4 + T lymphoc ytes, and the percentages of CD4 + T lymphocytes of the IL-4 mRNA + or IL-5 mRNA + cells were not affected. The antiinflammatory effect was non-specific. In addition, aerosol administration of dexamethasone enh anced IL-4 expression and methotrexate promoted eosinophil infiltratio n 12 h after challenge. Conclusion Aerosol administration of dexametha sone and methotrexate attenuated pulmonary Th2 reaction in ovalbumin s ensitized mice. Aerosol administration of drug exerts its effect at th e site of inflammation, which is more effective with less side effects . But at the beginning, aerosol administration might promote inflammat ion. In this way, oral or intravenous injection of glucocorticoids sho uld be given to moderate to severe asthmatic patients, and aerosol glu cocorticoids should be adminstered after the disease was under control . Methotrexate was less effective than dexamethasone but more irritati ve, and should not be given by inhalation, Intravenous injection of me thotrexate should be administrated to asthmatic patients who respond p oorly to glucocorticoids as an auxiliary therapeutic measure.