• Clinical and Experimental Pediatrics
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• v.56 no.1
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• pp.8-12
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• 2013

Asthma is associated with increased levels of eosinophils in tissues, body fluids, and bone marrow. Elevated levels of eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) have been noted in asthma patients. Higher levels of EDN and ECP are also associated with exacerbated asthmatic conditions. Thus, EDN, along with ECP, may aid the diagnosis and monitoring of asthma. Several groups have suggested that EDN is more useful than ECP in evaluating disease severity. This may partially be because of the recoverability of EDN (not sticky, 100% recovery rate), as ECP is a sticky and more highly charged protein. In terms of clinical utility, EDN level is a more accurate biomarker than ECP when analyzing the underlying pathophysiology of asthma. As a monitoring tool, EDN has shown good results in children with asthma as well as other allergic diseases. In children too young to fully participate in lung function tests, EDN levels may be useful as an alter native measurement of eosinophilic inflammation. EDN can also be used in adult patients and in multiple specimen types (e.g., serum, sputum, bronchoalveolar lavage fluid, and nasal lavage fluid). These results are repeatable and reproducible. In conclusion, EDN may be a novel biomarker for the diagnosis, treatment, and monitoring of asthma/allergic disease.

• Allergy, Asthma & Immunology Research
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• v.10 no.6
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• pp.686-697
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• 2018

Purpose: Several markers for eosinophilic inflammation have been proposed to predict response to asthma treatment. However, definitive criteria for treatment decisions have not yet been established. We investigate a potentially useful relatively non-invasive biomarker, eosinophil-derived neurotoxin (EDN), to predict favorable responses to budesonide or montelukast, common treatment for children with asthma. Methods: Young children (1 to 6 years old) were enrolled in this randomized, parallel, 2-group, open-label trial. Criteria for eligibility included: 1) being symptomatic during the run-in period; and 2) having a serum EDN (sEDN) level ${\geq}53ng/mL$, with positive specific immunoglobulin E to house dust mite. Eligible patients were randomly placed into 2 groups: the BIS group received budesonide inhalation suspension (BIS) 0.5 mg once daily; the MONT group received montelukast 4 mg once daily. Ineligible patients were invited to receive montelukast 4 mg once daily (OBS group). Treatment period was 12 weeks. Results: Asthma control days increased significantly in the BIS and MONT groups (P < 0.000) over the 12-week study period. There was no significant change in sEDN in the BIS group but there was a significant decrease in the MONT group (P < 0.000). Patients in the OBS group with high EDN levels (> 53 ng/mL) showed a significant decrease due to MONT treatment (P = 0.023). Rescue medication usage significantly decreased in the BIS and MONT groups (P < 0.000). Conclusions: EDN is a useful relatively non-invasive biomarker for predicting responses to montelukast and budesonide treatment of preschool children with beta2-agonist responsive recurrent wheeze and multiple-trigger wheeze (Trial registry at UMIN Clinical Trials Registry, UMIN000008335).

• Parasites, Hosts and Diseases
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• v.43 no.1 s.133
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• pp.33-37
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• 2005

Eosinophil degranulation is considered to be a key effector function for the killing of helminthic worms and tissue inflammation at worm-infected lesion sites. However, relatively little data are available with regard to eosinophil response after stimulation with worm-secreted products which contain a large quantity of cysteine proteases. In this study, we attempted to determine whether the degranulation of human eosinophils could be induced by the direct stimulation of the excretory-secretory products (ESP) of Paragonimus westermani, which causes pulmonary paragonimiasis in human beings. Incubation of eosinophils for 3 hr with Paragonimus-secreted products resulted in marked degranulation, as evidenced by the release of eosinophil-derived neurotoxin (EON) in the culture supernatants. Moreover, superoxide anion was produced by eosinophils after stimulation of the ESP. The ESP-induced EDN release was found to be significantly inhibited when the ESP was pretreated with protease inhibitor cocktail or the cysteine protease inhibitor, E-64. These findings suggest that human eosinophils become degranulated in response to P. westermani-secreted proteases, which may contribute to in vivo tissue inflammation around the worms.

• Parasites, Hosts and Diseases
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• v.46 no.2
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• pp.95-99
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• 2008

Eosinophil degranulation plays a crucial role in tissue inflammatory reactions associated with helminth parasitic infections and allergic diseases. Paragonimus westermani, a lung fluke causing human paragonimiasis, secretes a large amount of cysteine proteases, which are involved in nutrient uptake, tissue invasion, and modulation of hos's immune responses. There is, however, limited information about the response of eosinophils to direct stimulation by cysteine proteases (CP) secreted by P. westermani. In the present study, we tested whether degranulation and superoxide production from human eosinophils can be induced by stimulation of the 2 CP (27 kDa and 28 kDa) purified from excretory-secretory products (ESP) of P. westermani newly excysted metacercariae (PwNEM). A large quantity of eosinophil-derived neurotoxin (EDN) was detected in the culture supernatant when human eosinophils isolated from the peripheral blood were incubated with the purified 27 kDa CP. Furthermore, the 27 kDa CP induced superoxide anion production by eosinophils in time- and dose-dependent manners. In contrast, the purified 28 kDa CP did not induce superoxide production and degranulation. These findings suggest that the 27 kDa CP secreted by PwNEM induces superoxide production and degranulation of human eosinophils, which may be involved in eosinophil-mediated tissue inflammatory responses during the larval migration in human paragonimiasis.