The extract Ze 339 obtained from leaves of the petasin chemovariety (Petzell) inhibits the allergen induced Th-2 response and the hyper-reactivity in asthma

Objective

Epidemiological studies have shown that allergic rhinitis and allergic asthma often coexist in the same subject. The extract Ze 339 obtained by means of fluid CO² (sub-critical fluid extraction) from the leaves of Petasites hybridus L. has been proven active in allergic rhinitis. Therefore the question arose whether or not the extract will also be useful in allergic asthma. A murine model of allergeninduced airways inflammation is well elaborated [1, 2] with an increase in IL-4 and IL-5 in the bronchoalveolar lavage fluid (BAL), eosinophile recruitment into the lung tissue indicating that the allergic inflammation is driven by the activation of the T helper (Th) type 2 cells. Therefore the influence of Ze 339 in this model of allergic asthma was investigated.

Methods

Balb/c mice were immunised subcutaneously twice at weekly intervals with 0.4ml saline containing 1µg ovalbumine (OVA) and 1.6mg alums. Intranasal challenge was repeatedly performed (3 consecutive days) under light i.v. ketamine anaesthesia by applying 50µl OVA in alum-free saline solution (10µl) or saline as control.

Ze 339 was given at 10–30–100µg intra-nasally (in 40µl) just before the antigen challenge. The airway resistance was evaluated by whole-body plethysmography. Bronchial hyper-reactivity to aerosolized methacholine (100 mM, 1min) was investigated 24h after the last OVA challenge as readings of the mean airway constriction.

Results

Ze 339 inhibited the metacholine induced airway hyper-responsiveness (AHR) in a dose related manner. BAL was performed by cannulating the trachea and washing 4 times with 0.5ml each of ice-cold PBS 24h after the last antigen challenge. Ze 339 (100µg) significantly inhibited eosinophile recruitment into BAL. Corresponding with the reduction in recruitment the EPO activity in lung tissue was also decreased. Moreover, mucus hyper-production was significantly inhibited by 100µg of Ze339. The cytokines IL-4, IL-5 and RANTES in BAL were significantly reduced by 30µg Ze 339.

Conclusion

Topic administration of Ze 339 into the airway prior to antigen challenge in sensitized mice reduced hyper-reactivity and inhibited the production of Th2 IL-4 and IL-5, respectively, which might be important for the reduced eosinophil infiltration and chronic inflammation.

[1] Ohkawara Y et al.: Cytokine and eosinophil response in the lung, peripheral blood, and bone marrow compartments in a murine model of allergen-induced airway inflammation. Am J Res Cell Mol Biol 1997; 16: 510–520.

[2] Kips JC et al.: Murine models of asthma. Eur Respir J 2003; 22: 374–382.