Effect Of Echinococcus Granulosus Hydatid Cyst Fluid Protein On Allergic Rhinitis Induced By Ovalbumin In Mice

Background:Allergic rhinitis（AR）is a type I allergic disease caused by exposure to allergens,which is mediated by Ig E,infiltrated by eosinophils（EOS）in nasal mucosa and accompanied by increased secretion of Th2 cytokines.Its main symptoms are itchy nose,stuffy nose,runny nose and sneezing.AR is one of the most common allergic diseases in the world.In recent decades,the incidence rate（10% 40%）is on the rise,which seriously affects the quality of life of patients."Hygienic hypothesis" shows that worm infection can immunomodulate the host through complex mechanisms.Studies have shown that worm infection can inhibit the occurrence and development of allergic diseases,and there is a negative correlation between them.Because worm infection can cause parasitic diseases and related pathological damage,it is clinically limited to treat related diseases with worm infection.Echinococcus granulosus is parasitic in animal or human liver,lung,brain and other tissues and organs.In various animal models of autoimmune and allergic diseases,Echinococcus granulosus infection and its derived proteins can improve the inflammatory response of allergic diseases,suggesting that it can induce the host immune system to produce a strong immunosuppressive effect.AR is an allergic disease with Th2 cell immune response as the main factor.At present,there are few related researches on worm and its derivatives.In this study,we explored the effect of hydatid cyst fluid protein（HCFP）on the inflammatory response of AR mice,and analyzed its immunological mechanism,so as to provide a basis for the subsequent treatment of immune disorders with this protein.Objective:To investigate the protective effect of Echinococcus granulosus（E.granulosus）hydatid cyst fluid protein（HCFP）on ovalbumin（OVA）-induced allergic rhinitis（AR）in mice.Methods:Twenty-four BALB/c mice at ages of 8 to 10 weeks,each weighing approximately 20 g,were randomly divided into four groups,including groups A（blank control group）,B（blank intervention group）,C（AR model group）and D（AR+HCFP intervention group）,with 6 mice in each group.On days 0,2,4,6,8,10 and 12,mice in groups A,B,C and D were injected with 200 μL sterile PBS,200 μL sterile PBS containing 20 μg HCFP,200 μL sterile PBS containing 50 μg OVA and 5 mg Al（OH）3 gel,and 200 μL sterile PBS containing 50 μg OVA,5 mg Al（OH）3 gel and 20 μg HCFP,respectively.On days 14 to 20,mice in groups A,B,C and D were administered with 40 μL sterile PBS,40 μL sterile PBS containing 20 μg HCFP,40 μL sterile PBS containing 2 mg OVA and 40 μL sterile PBS containing 2 mg OVA and 20 μL HCFP by nasal drop,respectively.Mouse behavioral changes were observed and behavioral scores were estimated.The serum levels of interferon-γ（IFN-γ）,interleukin-4（IL-4）,IL-5,IL-10,TGF-β and OVA-specific Ig E（OVA-s Ig E）were measured using enzyme-linked immunosorbent assay（ELISA）,and the pathological changes of mouse nasal mucosa were observed by hematoxylin and eosin（HE）staining.Results:The mean behavioral score was significantly greater in Group C（6.83 ± 0.50）than in groups A（1.17 ± 0.52）and B（1.33 ± 0.52）（P < 0.05）,while a lower mean behavioral score was estimated in Group D（3.50 ± 0.50）than in Group C（P < 0.05）.There were significant differences among the groups in terms of serum IFN-γ（F = 4.08,P < 0.05）,IL-4（F = 275.90,P < 0.05）,IL-5（F = 96.82,P < 0.05）,IL-10（F = 77.67,P < 0.05）,TGF-β（F = 9.98,P < 0.05）and OVA-s Ig E levels（F = 44.69,P < 0.05）.The serum IFN-γ level was significantly lower in Group C than in groups A,B and C（P < 0.05）,and the serum levels of IL-4,IL-5 and OVA-s Ig E were significantly higher in Group C than in groups A,B and C（P < 0.05）,while the serum IL-10 and TGF-β levels were significantly greater in Group D than in Group C（P < 0.05）.Microscopy showed apparent loss of nasal mucosa cilia,increased number and enlargement of goblet cells,interstitial edema and submucous vascular dilation in Group C,while the pathological changes of nasal mucosa were alleviated in Group D relative to Group C.Conclusions:1.E.granulosus HCFP reduced OVA-induced nasal mucosa injury in mice;2.E.granulosus HCFP can stimulate regulatory cytokines,correct Th1/Th2 imbalance,and play an anti-allergic role in AR model mice,which indicates that it can be applied to the clinical treatment of AR.