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العنوان
The effect of Interleukin-2 on Psoriasis-like Skin Inflammation Induced in the experimental mice by Imiquimod /
المؤلف
Salman, Samar Mohammed Salah El-dein Basiony.
هيئة الاعداد
باحث / سمر محمد صلاح الدين بسيوني سالمان
مشرف / اماني محمد عبداللطيف
مناقش / محمد لبيب سالم
مناقش / ياسمينه احمد العطار
الموضوع
Dermatology. Venereology.
تاريخ النشر
2019.
عدد الصفحات
101 p. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
الأمراض الجلدية
تاريخ الإجازة
20/11/2019
مكان الإجازة
جامعة طنطا - كلية الطب - Dermatology and Venereology
الفهرس
Only 14 pages are availabe for public view

from 141

from 141

Abstract

Psoriasis vulgaris is a common chronic inflammatory skin condition, immune mediated that occurs in genetically susceptible individuals (1). Plaque psoriasis, the most common disease variant, which is seen in approximately 85% of cases, commonly manifests as erythematous plaques with thick scaling on the extensor surfaces, trunk, and scalp (2). Although early concepts of the pathogenesis of psoriasis focused primarily on keratinocyte hyperproliferation, dysregulation of the immune system is now recognized as a critical event in this disease. The evolving knowledge of the role of the immune system in psoriasis has had a significant impact on treatment development. Many new and emerging therapeutic agents target specific immunologic aspects of psoriatic disease(1). The paradox was first merged in 1993, when it was discovered that knockout of the gene encoding IL 2 in mice led to severe lymphoproliferation and autoimmunity, rather than the predicted immune deficiency. This finding was soon followed by the description of similar phenotypes of mice with a knockout of the gene encoding the β-chain of the IL 2 receptor {IL 2Rβ; hereafter referred to as CD122) or IL 2Rα thereafter referred to as CD25} (3). This was confirmed by showing that TReg cells are absent in IL 2 or IL 2R deficient mice, and that adoptive transfer of these cells from normal mice would prohibit autoimmunity in the deficient mice. Thus, IL-2 that had been used for decades to stimulate effector T cells turned out to be inhibitory of these cells, and instead is required for activation of the TReg cells that suppress effector T cells (4). IL 2 has been shown to promote the development of naive CD4+ T cells into peripherally derived TReg cells, T helper (TH2) cells, TH9 cells and, in some studies, TH1 cells31. By contrast, IL 2 suppresses the differentiation of CD4+ T cells into TH17 cells and T follicular helper (TFH) cells (5). The aim of the work was to assess the effect of anti IL2/IL-2 mix vs low dose of IL2 on psoriasis like skin inflammation induced by imiquimod in mouse model and its effect on TReg. In this study, a total of 35 male mice were included in this study and divided into the following five groups (n = 7/group): group I, seven mice with psoriasis like skin disease that were treated with mix of IL2 and anti-IL2 antibody. group II; seven mice with psoriasis like skin disease that were treated with low dose of IL2 group III, seven mice with psoriasis like skin disease that were treated with topical steroids; group IV, consists of seven mice with psoriasis like skin disease, with no treatment. group V, consists of seven naïve mice without manipulation; The Psoriasis like model was constructed after shaving dorsal skin of the mice and a commercially available 5% IMQ cream (Aldara, 3M Pharmaceuticals) was applied with daily topical dose of 62.50 mg of the IMQ cream on the shaved area of their backs for successive sex days, this translates into a daily dose of 3.125 mg of the active ingredient. Then, after 7 days treatment protocols were used while applying simultaneously aldara cream, Il2 or il2/ antiil2 complex were given in equal doses by intraperitoneal injections for successive three days and 4 treatment free days after. Finally, all mice groups were sacrificed when blood samples and skin biopsies were gathered, The results of this study revealed the following: 1. Phenotype change of the experimental mice: The macroscopic appearance of the skin was observed at the end of the experiment. The skin of mice of control group showed the normal smooth appearance of the skin after shaving the hair, while the group treated with anti IL-2/IL-2 complex showed some improvement after three days of treatment and marvelous response after seven days with disappearance of the scales and erythema and decrease in the scratch behavior frequencies, on contrast to topical steroids treated groups, and also in contrast to control group (gr IV) 2. Histopathological examination of all studied groups: The group treated with anti IL-2/ IL-2 complex showed excellent improvement after seven days from the onset of therapy with decrease of the skin thickness, and lymphocytes infiltration. The group received the standard treatment showed minimal improvement with the same pathologic criteria of the model. On the other hand, the group received IL-2 therapy showed marked improvement but with lesser degree than that of the anti IL-2/IL-2 mix. 3. Morphometric analysis of the mean thickness of the epidermis The mean thickness of the epidermis in most of skin lesions showed significant decrease in comparison to Ps lesions, in antiIl-2/IL-2 complex group followed by IL-2 group which was confirmed by our morphometric study, in comparison to topical steroids treated group. 4. Flowcytometry results from withdrawn blood samples: CD4+ve Foxp3+ve showed highly significant increase in anti IL2/il2 complex, then IL-2 group came after and the naïve group, then finally the group that received the standard therapy. CD25 was positive in all studied mice and showed the highest significant increase in anti IL2/il2 complex group. Also, the IL-2 group came after.