Effects of pranlukast on ovalbumin induced early-phase bronchoconstriction in guinea pigs

Lee, Sin Hyung; Shim, Jae Jeong; Kim, Kyung Kyu; Jeong, Hye Cheol; Kwon, Young Hwan; Kim, Je Hyeong; Lee, Sung Yong; Lee, So Ra; Lee, Sang Youb; Cho, Jae Youn; In, Kwang Ho; Yoo, Se Hwa; Kang, Kyung Ho

Abstract

BACKGROUND: Leukotriene (LT) C4, D4, and E4, the main components of slow-reacting substance of anaphylaxis (SRS-A), have been suggested to play an important role in bronchial asthma such as antigen- induced bronchoconstriction, airway hyperreactivity, and pulmonary eosinophil accumulation. The purpose of this study was to evaluate the effects of treatment with the cysteinyl-LTs (cys-LTs) antagonist, pranlukast on allergen-induced guinea pig asthma model.
METHODS
Guinea pigs of treatment and placebo groups were sensitized by subcutaneous injection of ovalbumin (OVA) and challenged by inhalation of aerosolized OVA (1% weight/volume OVA). Normal control group did not sensitize with OVA. Oral ingestion of pranlukast and normal saline to the treatment and placebo groups was performed. In the treatment and placebo groups, airway resistance was measured before and after oral ingestion. Serum LTC4 and eosinophilic infiltration of the bronchiolar and peribronchiolar tissues were measured after ingestion in the treatment and placebo groups.
RESULTS
Allergen-induced airway constriction developed in 20 (8 in treatment group, 12 in placebo group) among 35 guinea pigs. Airway resistance was significantly decreased at 3 and 6 minutes after OVA challenge in the pranlukast treatment group. In the placebo group, there was no difference of airway resistance between before and after saline ingestion. Serum LTC4 levels showed 348.4 pg/ml in the treatment group, 373.9 pg/ml in the placebo group, and 364.4 pg/ml in the control group. There were no statistically significant difference between treatment and placebo group (p=0.232), and treatment and control group (p=0.501). Eosinophilic infiltrations in the peribronchiolar region per one-microscopic field (X400 high power fields) demonstrated 7.06 in the treatment group, 19.2 in the placebo group, and 4.50 in the control group. There was significant decrement of eosinophilic infiltration in the treatment group which was compared with placebo group (p=0.001).
CONCLUSION
These results demonstrate that pranlukast, a cys-LTs receptor antagonist, can attenuate allergen induced early-phase bronchoconstriction and eosinophilic infiltration in the bronchiolar tissues.