Effect of suplatast tosilate (IPD-1151T) on a mouse model of asthma: inhibition of eosinophilic inflammation and bronchial hyperresponsiveness.
BACKGROUND
Suplatast tosilate (IPD) is a newly developed 'anti-allergic' drug. It seems to be a unique compound because of its ability to suppress IgE but not IgG or IgM production in vivo and cytokine production from type 2 helper T cells (Th2) in vitro. However, information on its in vivo effect on an animal model of asthma is limited.


METHODS
BALB/c mice sensitized to ovalbumin (3 times, 2-week interval) were challenged with ovalbumin by inhalation (50 mg/ml for 20 min, once a day for 6 days). In this study, we explored the influence of IPD on eosinophil infiltration into the airways, bronchial hyperresponsiveness (BHR) to methacholine, specific IgE antibody production, and cytokines in bronchoalveolar lavage fluid (BALF) using this murine model.


RESULTS
Treatment with IPD significantly reduced the number of total cells and eosinophils in BALF (around -40%) and almost completely inhibited the development of antigen-induced BHR. Histological findings confirmed the reduction of submucosal cell infiltration in the lung, and disclosed the marked inhibition of bronchial epithelial cell damage. Ovalbumin-specific IgE was slightly but significantly reduced. The levels of IL-4, IL-5 and IL-13 in BALF were significantly decreased in mice treated with the compound compared to those in untreated mice.


CONCLUSIONS
These results suggest that IPD is capable of inhibiting the production of Th2 cytokines, which inhibit eosinophil infiltration into the murine airway, IgE synthesis, and development of BHR, in a murine model of asthma.
Zhao
G D
GD
Second Department of Internal Medicine, Ehime University School of Medicine, Onsen-gun, Ehime, Japan.
Yokoyama
A
A
Kohno
N
N
Sakai
K
K
Hamada
H
H
Hiwada
K
K
D000818:Animals; D018926:Anti-Allergic Agents / Q000627:therapeutic use*; D001190:Arylsulfonates / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000517:prevention & control*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D008168:Lung / Q000473:pathology; D016210:Methacholine Chloride; D051379:Mice; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D013452:Sulfonium Compounds / Q000627:therapeutic use*
D018926:Anti-Allergic Agents; D001190:Arylsulfonates; D016207:Cytokines; D007074:Immunoglobulin G; D013452:Sulfonium Compounds; D016210:Methacholine Chloride; D007073:Immunoglobulin E; D010047:Ovalbumin; C073028:suplatast tosilate