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薬理と治療
Abstract
[Objectives The influence of histamine H1 receptor antagonists on the function of osteopontin(OS)was examined in vitro. We also examined the influence of epinastine hydrochloride (EP)on the appearance of OS in nasal secretions obtained from Japanese cedar pollinosis patients treated with EP during the pollen season. Methods BEAS-2B cells(5×105 cells/mL)were stimulated with 100 ng/mL TNF-α in the presence of various concentrations of histamine H1 receptor antagonists, fexofenadine hydrochloride(FEX), EP, azelastine hydrochloride(AZ)and ketotifen fumarate salt(KET)for 24h. OS levels in culture supernatants were examined by ELISA. BEAS-2B cells were also stimulated with 330 ng/mL OS in the presence of either FEX, EP, AZ or KET. After 24 h, the levels of cytokines, INF-γ, IL-4 and IL-5 in the culture supernatants were examined by ELISA. Nasal secretions were obtained from pollinosis patients treated with EP once a day at a single dose of 20 mg for two weeks. OS levels in nasal secretions were also examined by ELISA. Results The addition of histamine H1 receptor antagonists into BEAS-2B cell cultures caused significant suppression of OS production from cells induced by TNF-α stimulation. Histamine receptor antagonists examined in this study also inhibited the ability of BEAS-2B cells to produce IL-4 and IL-5, but not INF-γ, in response to OS stimulation. The minimum concentration that caused significant suppression of OS and cytokine production was nearly identical to their therapeutic blood levels. Oral administration of EP into pollinosis patients also inhibited OS concentrations in nasal secretions. Conclusions These results may suggest that histamine H1 receptor antagonists modulates the function of OS, and exerts therapeutic effects on allergic diseases, especially pollinosis., Objectives The influence of histamine H1 receptor antagonists on the function of osteopontin(OS)was examined in vitro. We also examined the influence of epinastine hydrochloride (EP)on the appearance of OS in nasal secretions obtained from Japanese cedar pollinosis patients treated with EP during the pollen season. Methods BEAS-2B cells(5×105 cells/mL)were stimulated with 100 ng/mL TNF-α in the presence of various concentrations of histamine H1 receptor antagonists, fexofenadine hydrochloride(FEX), EP, azelastine hydrochloride(AZ)and ketotifen fumarate salt(KET)for 24h. OS levels in culture supernatants were examined by ELISA. BEAS-2B cells were also stimulated with 330 ng/mL OS in the presence of either FEX, EP, AZ or KET. After 24 h, the levels of cytokines, INF-γ, IL-4 and IL-5 in the culture supernatants were examined by ELISA. Nasal secretions were obtained from pollinosis patients treated with EP once a day at a single dose of 20 mg for two weeks. OS levels in nasal secretions were also examined by ELISA. Results The addition of histamine H1 receptor antagonists into BEAS-2B cell cultures caused significant suppression of OS production from cells induced by TNF-α stimulation. Histamine receptor antagonists examined in this study also inhibited the ability of BEAS-2B cells to produce IL-4 and IL-5, but not INF-γ, in response to OS stimulation. The minimum concentration that caused significant suppression of OS and cytokine production was nearly identical to their therapeutic blood levels. Oral administration of EP into pollinosis patients also inhibited OS concentrations in nasal secretions. Conclusions These results may suggest that histamine H1 receptor antagonists modulates the function of OS, and exerts therapeutic effects on allergic diseases, especially pollinosis.]
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