Montelukast Reduces Serum Levels of Eosinophil-Derived Neurotoxin in Preschool Asthma

Kim, Chang-Keun; Callaway, Zak; Park, Jin-Sung; Nishimori, Hisashi; Ogino, Tikatoshi; Nagao, Mizuho; Fujisawa, Takao

In previous asthma 12 and AD 23 studies, sEDN levels have correlated well with symptom scores. It is known that eosinophils release EDN and other degranulation products when activated; in particular, peripheral blood eosinophils were found to release approximately 17%-28% of their total intracellular EDN. 24 Furthermore, Sedgwick et al. 24 demonstrated that intracellular EDN is also increased in asthmatic patients, while ECP is not. Montelukast is an LTRA, capable of binding with cysteine leukotriene (cysLT) receptors expressed on eosinophils and disrupting their autocrine release. CysLTs can induce eosinophil degranulation, 25 which then leads to release of a number of mediators including EDN, ECP and cysLTs. 26 This may explain the reduction in EDN levels in the MONT group and in patients in the OBS group with high EDN levels. Corticosteroid treatment may or may not eliminate cytokine-primed, EDNincreased and longer-surviving eosinophils resulting in decreased EDN levels. 12 We observed no significant decrease in EDN levels after budesonide treatment in our study, which was contrary to our initial hypothesis that budesonide would also reduce EDN levels. This may be because budesonide, an ICS, acts locally, whereas montelukast acts systemically. Eosinophils develop principally in the bone marrow and are recruited from the circulation, where they migrate to inflammatory sites, such as the airways, and then participate in immunologic processes. 26 Once activated, the eosinophil releases EDN and other granular proteins. Changes in granular protein levels signal changes in the turnover and activity of the eosinophil. Taken together, eosinophil production, recruitment and activation are a systemic process.