The Experimental Study Of The Curative Effect Of Anti-IL-33 Monoclonal Antibody On Balb/c Mouse Atopic Dermatitis Model

Introduction: Atopic dermatitis(AD)is a common recurrent chronic inflammatory dermatosis characterized by pruritus,pleomorphic lesions and exudative tendency.Currently,the main pathogenesis of AD involves genetic factors,skin barrier dysfunction,Th1/Th2 cell imbalance and infection factors.Interleukin-33(IL-33)plays a dual role in both regulating gene transcription in the nucleus and inducing TH2-type cytokine gene expression,regulating Th2-mediated immune response and involving inflammation through being secreted outside the extracellular and connecting with homolog of sulfotransferase(ST2),involved in inflammation.Objective: To investigate whether anti-IL-33 monoclonal antibody has a therapeutic effect on AD induced by 2,4-dinitrochlorobenzene(DNCB)in miceMethods: 24 female balb/c mice were divided into 4 groups:(1)negative control group(n=6): mice were stimulated with vehicle but not DNCB and then treated with PBS one hour later;(2)positive control group(n=6): mice were stimulated with DNCB to induce atopic dermatitis and then treated with PBS one hour later;(3)anti-IL-33 treatment group(n=6): mice were stimulated with DNCB first and then treated with anti-IL-33 monoclonal antibody one hour later;(4)tacrolimus treatment group(n=6): mice were stimulated with DNCB first and then treated with tacrolimus one hour later.The experimental period was 33 days.The dynamic changes of skin lesions,pruritus score,thickness of mouse ears and dermatitis score were examined.Results: Positive control mice had obvious dermatitis symptoms,increased pruritus scores,thickened ears,increased dermatitis score,thickened epidermis,increased numbers of eosinophils and mast cells,increased total serum IgE,and had significant difference comparing with the negative control group(P <0.01).The pathological changes of mice skin tissue were observed under light microscope and the changes of epidermal thickness,eosinophil and mast cell infiltration were calculated and the total serum IgE level was detected by ELISA at the end of experiment.IL-33-treated and tacrolimus-treated mice had improved dermatitis symptoms,decreased pruritus scores,thinner ears,reduced dermatitis scores,thinner epidermis,decreased number of eosinophils and mast cells,and decreased serum total IgE.Besides,the improvement of anti-IL-33-treated mice was more obvious than tacrolimus treated mice and these two treatment groups both had statistically significant difference comparing with negative control group(both P <0.01).The pathological results showed acanthosis,infiltrated inflammation cell and significant increased number of the eosinophils,lymphocytes and mast cells in skin lesion of positive control mice comparing with the negative control group(P <0.01).After treatment,the pathological changes in the anti-IL-33 treatment group and tacrolimus treatment group were both significant lighter than the positive control group,and the pathological inflammatory changes improved greater in the anti-IL-33 treatment group than the tacrolimus treatment group.The skin in the negative control mice was normal.Conclusion: Anti-IL-33 mAb has a therapeutic effect on DNCB-induced AD in mice.