| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Research Center, Mochida Pharmaceutical Co., Ltd., Shizuoka, Japan
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-
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- 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.
This article has been cited by other articles:
|
|
 |
|
  Y. Chiba, S. Nakazawa, M. Todoroki, K. Shinozaki, H. Sakai, and M. Misawa Interleukin-13 Augments Bronchial Smooth Muscle Contractility with an Up-Regulation of RhoA Protein Am. J. Respir. Cell Mol. Biol., February 1, 2009; 40(2): 159 - 167. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Chiba, J. Arima, H. Sakai, and M. Misawa Lovastatin inhibits bronchial hyperresponsiveness by reducing RhoA signaling in rat allergic asthma Am J Physiol Lung Cell Mol Physiol, April 1, 2008; 294(4): L705 - L713. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Negishi, Y. Kato, O. Ooneda, J. Mimura, T. Takada, H. Mochizuki, M. Yamamoto, Y. Fujii-Kuriyama, and S. Furusako Effects of Aryl Hydrocarbon Receptor Signaling on the Modulation of Th1/Th2 Balance J. Immunol., December 1, 2005; 175(11): 7348 - 7356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Edwan, G. Perry, J. E. Talmadge, and D. K. Agrawal Flt-3 Ligand Reverses Late Allergic Response and Airway Hyper-Responsiveness in a Mouse Model of Allergic Inflammation J. Immunol., April 15, 2004; 172(8): 5016 - 5023. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Kudlacz, C. J. Andresen, M. Salafia, C. A. Whitney, B. Naclerio, and P. S. Changelian Genetic Ablation of the src Kinase p59fynT Exacerbates Pulmonary Inflammation in an Allergic Mouse Model Am. J. Respir. Cell Mol. Biol., April 1, 2001; 24(4): 469 - 474. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. Van Wauwe, F. Aerts, M. Cools, F. Deroose, E. Freyne, J. Goossens, B. Hermans, J. Lacrampe, H. Van Genechten, F. Van Gerven, et al. Identification of R146225 as a Novel, Orally Active Inhibitor of Interleukin-5 Biosynthesis J. Pharmacol. Exp. Ther., November 1, 2000; 295(2): 655 - 661. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
