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pp.82-102
The inhibitory effects of water extract of Cortex Mori(CM) was investigated for allergic asthma in a mouse model. Experimental allergic asthma was induced by repeated intraperitoneal sensitization and aerosol challenge of ovalbumin (OVA). CM extract (10mg/mouse/day) was administrated orally whereas control mice were given with identical volume of phosphate-buffered saline (PBS) for 7 days during the course of challenge. When airway hyperreactivity(AHR) measured by β-methacoline-induced airflow obstruction was compared, AHR of CM-treated mice was significantly lower than those of control mice, indicating that CM extract can attenuate an asthmatic symptom. Airway recruitment of leukocytes and cytokine levels in broncho-alveolar lavage fluid (BALF) was analyzed in order to evaluate CM effect on pulmonary inflammation. Total number of leukocytes in BALF was lower in CM-treated mice than in control without significance. Interestingly, CM treatment elevated a distribution of eosinophils which are crucial in asthmatic response. However, comparison of absolute number showed that it resulted from a decrease of total leukocyte and macrophage numbers. Levels of type 2 (Th2) cytokines (IL4, IL5 and IL 13) measured by ELISA in BALF were not significantly reduced by CM and IFN-γ, a type 1 (Th1) cytokine, was also comparable between two groups, indicating that CM treatment has little or no effect on airway inflammation and secretion of relevant cytokines. For an insight into the mechanism of CM effect on AHR, immunemodulatory activity of CM was analyzed at a cellular level. Peribronchial lymph node(LN) cells and lung-infiltrating lymphocytes (LIL) collected from CM-treated and control mice were in vitro stimulated with OVA antigen. Although there was no significance, number of LN cell and LIL was higher in CM-treated mice than controls and their Ag-specific proliferative response (3H-TdR uptake assay) was similar. Production of Th2 cytokine, IL 5 and IL 13 was relatively enhanced, but without statistical significance, while IFN-γ production was minimally altered in CM-treated mice. Immunemodulation of CM in the field of humoral immunity, antibody levels in serum were measured and compared. No significant difference was observed in the levels of IgE. However, levels of type 1 and 2 antibody IgG2a and IgG1 were signifcantly enhanced by CM treatment. As CM-mediated alleviation of AHR was not clearly explained by above results, degranulation of eosinophils was finally examined by their release of peroxidase. Levels of peroxidase in BALF was significantly lower in CM treated mice, suggesting that CM inhibits in vivo degranulation of eosinophils, although its effect was not shown during their in vitro incubation. Taken together, data from current study indicate CM extract alleviates AHR through inhibition of eosinophil degranulation rather than any immunological regulation. Instead, immunemodulatory activity of CM is likely to be adversely effective in (Th2)
