We have found a novel
anti-allergic agent,
M50367, which suppresses
IgE biosynthesis and eosinophil accumulation in vivo. In this study, we evaluated the ability of
M50367 to modulate Th1/Th2 balance in Th2-background BALB/c mice and to inhibit
airway hyperresponsiveness in a murine model of atopic
asthma. Oral
M50367 at 3-30 mg/kg/day exhibited 51 to 73% reduction of IL-4/IL-5 production and 2- to 5-fold augmentation of IFN-gamma production by Ag-stimulated cultured splenocytes of the mice sensitized with DNP-Ascaris. These alterations in Th1/Th2
cytokine production were accompanied by 55-85% suppression of plasma
IgE level. Oral
M50367 at a dose of 10 mg/kg/day significantly inhibited Ig-independent peritoneal
eosinophilia by 54%, which was induced by repeated i.p.
injections of Ascaris suum extract. To develop
airway hyperresponsiveness caused by allergic airway
inflammation, BALB/c mice were sensitized with i.p. OVA
injections, followed three times by OVA inhalation. Oral
M50367 significantly inhibited the increase in airway reactivity to
acetylcholine, together with the elevation of plasma
IgE level and
pulmonary eosinophilia, which were observed in vehicle-treated mice 1 day after the last inhalation. Moreover,
M50367 treatment reduced
IL-4 and
IL-5 production and tended to enhance IFN-gamma production, not only by cultured splenocytes, but also in bronchoalveolar lavage fluid. These results suggest that
M50367 has a modulating ability of Th1/Th2 balance to down-regulate Th2 response in the circulating system as well as at the sites of
inflammation, and may be beneficial for the treatment of allergic disorders such as atopic
asthma.