Bronchial asthma is characterized by chronic airway
inflammation. Eosinophils are involved in airway
inflammation and play crucial roles in
asthma. There is accumulating evidence to suggest contributions of cysteinyl
leukotrienes (cysLTs) and
thromboxane (TX) A(2) to the recruitment of eosinophils into lung in asthmatics.
KP-496 is a novel dual antagonist for CysLT receptor type 1 and TXA(2) receptors. The aim of this study was to evaluate the anti-inflammatory effects of
KP-496 on
Sephadex-induced airway
inflammation.
Sephadex suspension was intratracheally injected into rats. Amounts of regulated on activation, normal T cell expressed and secreted (
RANTES) and eotaxin, and numbers of infiltrating cells in bronchoalveolar lavage fluid were measured 24 and 48 h after
Sephadex injection, respectively.
KP-496 (30, 100 microg/head) was intratracheally administered to rats 1 h before and 7 h after
Sephadex injection.
KP-496 and
prednisolone (10 mg/kg, per os) exhibited significant inhibitory effects on infiltration of total cells and eosinophils into lung. Production of
RANTES was significantly inhibited by
KP-496 and
prednisolone. Production of eotaxin was significantly inhibited by
prednisolone.
KP-496 also inhibited the production of eotaxin, though this effect was not significant. These results demonstrate that
KP-496 exhibited the anti-inflammatory effects by inhibiting infiltration of inflammatory cells and productions of
RANTES and eotaxin.