الفهرس 
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Abstract
Asthma is a chronic inflammatory disease of the airways and related with airway narrowing in response to triggers. It was reported that 300 million individuals worldwide had asthma, and anticipated that this number would increase to 400 million by 2025. The current study aimed to enhance the anti- allergic effect of DEC which is anti-filarial drug with strong anti-inflammatory and anti-allergic properties using anti DEC-antibody combined with DEC and DEC combined with quercetin which is a strong anti-inflammatory natural drug. DEC is potential to treat asthma because of its interference with arachidonic acid metabolism. The current study used passive immunization of anti-DEC-antibody in asthmatic mouse model. Previous studies used anti-DEC antibodies to delay the clearance of DEC from the blood or increase antibody binding to deposited DEC in microfilarial bodies and hence potentiates its action against microfilaria. Polyclonal antibodies to the drug was developed by intramascular admenistration of MPCA (methyl piperazine carboxylic acid, an acid hydrolysis product of DEC) in rabbits and the antibodies were then passively immunized to the mice, anti-BSA Ab was used as a control to anti-DEC Ab. Quercetin is a flavonoid that is naturally found in many fruits and vegetables and has been shown to exert multiple biological effects in experimental models, including the reduction of major symptoms of asthma. The current study used drug combination since it is widely used for treating several chronic diseases due to its efficacy to potentiate the therapeutic effect and reduces toxicity and dosage.
(VI) The mice model of asthma was developed by egg ovalbumin as an allergen after intradermal sensitization. Mice were divided into 8 groups (16 mice/ group): (I) Control, (II) Ova (untreated), (III) Ova (DEC-treated), (IV) Ova (Passively immunized with anti-BSA antibodies followed by DEC-treatment), (V)
(VII) Ova(Passively immunized with anti-MPCA antibodies followed by DEC-treatment), (VI) Ova [DEC and quercetin (10 mg/ Kg)-treated], (VII) Ova [DEC and quercetin (20 mg/ Kg)-treated] and (VIII) Ova [DEC and quercetin (40 mg/ Kg) - treated]. Control group was exposed to vehicles only, while allergic airway inflammation model was used in the groups II-VIII through intradermal sensitization with 100 μl 0.3% ovalbumin in corn oil at 31 and 33 days followed by an exposure to 0.3% ovalbumin aerosol in normal saline for 30 min by ultrasonic nebulizer at 43, 50, 53 and 54 days. DEC was given orally at 10 mg/ Kg, while anti- BSA or MPCA antibodies were injected intraperitoneally (0.5 ml/ mouse).
At day 55, the mice were euthanized by a lethal dose of pentobarbital. Serum, BALF and lung tissue homogenates were collected and stored at -80°C. In addition equal pieces from both sides of lung tissue from each animal was fixed in10% formaline solution for 24 hr and later tissues were prepared for microscopic examination. Inflammatory markers such as IL-4, IL-5, IFN-γ, and OVA- specific IgE levels was detected in serum using ELISA. EPO and lung tissue eotaxin 2 were measured in lung tissue homogenates while total IgE was measured in BALF. Histopathological alterations was examined in lung tissue.
The obtained data revealed that passive immunization with anti-DEC Ab did not potentiate the anti-allergic effect of DEC. However, the ELISA test could show the specific reaction to accumulated DEC in DEC-Ova with respect to Ova. The increased serum levels of IL-4, IL-5, and total BALF IgE in Ova-αBSA-DEC group with respect to ova-DEC and ova-αDEC-DEC groups, indicated that this Ab could abrogate the anti-allergic effect of DEC. Furthermore, histological examination showed the same effect of anti-BSA Ab as illustrated by increased leukocyte infiltration. Indeed, the secretion of Th2 cytokines (IL- 4 and IL-5) and
increased infiltration of leukocytes in the tissue were found to associate with increased IgE. This could imply the necessity of adsorption techniques before Ab
applications to overcome the cross reactivity of this Ab with BSA which increased the allergic reactions. On the other hand, Qur at 40 mg/ Kg could be recommended to potentiate DEC effect because of the reduction of IL-4, IL-5, IgE, EPO, eotaxin 2 levels and obviously recovered inflammatory reactions in the lung tissue in comparison to ova-DEC group. This dose also showed significant potentiation for DEC effect to reduce tissue EPO and eotaxin2 which are diagnostic markers for tissue eosinophilia. Moreover, the present data illustrated the potentiating effects of different doses of Qur with DEC for reduction of the IL-4 cytokine produced from the CD4+ Th lymphocytes; therefore ratio of IFN-g/IL-4 retained to control level effect.
In conclusion, Passive immunization with anti-DEC Ab did not potentiate the anti-allergic effect of DEC. This can be referred to the presence of a reactive fraction of this Ab with BSA which increased the allergic reactions. This could imply the necessity of adsorption techniques before Ab applications. On the other hand, Qur at 40 mg/ Kg could be recommended to potentiate DEC effect suggesting its potential as a novel approach for treatment.