Investigation of effects of royal jelly on autoimmunity in autoimmune thyroid diseases

71 8- SUMMARY INVESTIGATION OF EFFECTS OF ROYAL JELLY ON AUTOIMMUNITY IN AUTOIMMUNE THYROID DISEASES Among autoimmune thyroid diseases, Basedow-Graves' disease is the most frequent cause seen in hyperthyroidism. Graves' disease is an organ-specific autoimmune disease with unknown etiology. TSHR Ab plays the most important role for the pathogenesis of Graves' disease. Hyperthyroidism and goiter occur when the antibody stimulates excessively for TSH receptor. Recently, role of cytokines for the pathogenesis of Graves' disease has been studied extensively. Royal jelly (RJ) is a creamy product secreted by young nurse worker bees (Apis mellifera) and it is synthesized in the hypopharyngeal and mandibular glands. RJ has been reported to have such pharmacological characteristics as anti-tumor, anti bacterial, anti-hypercholesterolemic, anti-allergic, anti-inflammatory, immunomodulatory, insulin-like, anti-fatigue properties. Major aim of the present study is to evaluate the effect of RJ on autoimmunity in peripheral lymphocyte culture and to establish the therapeutic doses. In the first phase, lymphocyte cell isolation from 4 voluntary healthy subjecs was performed to find effective concentration on immunity (stimulation, inhibition or immunomodulation). Serial dilutions of the RJ were prepared (0-500 mg/ml). Each isolated lymphocyte cells were treated with above diluted samples. MTT test was carried out after incubation of 72 hours. In the second phase, 6 patients with Graves' disease who newly diagnosed by clinical and laboratory methods admitted to Endocrinology and Metabolic Disease Clinic of Medical Faculty, K.T.U and untreated.72 RJ samples of 0, 25 and 400 mg/ml were incubated in a culture medium for 72 hours with isolated lymphocytes obtained from the patients. After incubation, MTT test in lymphocyte cell culture, Thl cytokines IFN-y, TNF-a and IL-12, and Th2 cytokines IL-4 and IL-10 levels by E ASIA method, TSHR Ab by radioreceptor method were determined. Concentration affecting lymphocytes to proliferate was found to be 400 mg/ml by MTT test after incubation of 72 hours in cell culture medium. Of cytokines produced and secreted from lymphocytes IFN-y increased, whereas, other cytokines decreased as RJ concentration increases. Significant differences according to RJ concentration were found only for IFN-y and TNF-a. IL-4 concentrations were kept at border of significancy. Of Thl/Th2 cytokines ratios which they are important markers for activation and remission periods of Graves' disases, IFN-y/IL-4 and IFN-y/IL-10 ratios were also exhibited significant differences with various RJ concentrations. RJ treatment in lymphocytes from patients with Graves' disease was shifted the Thl/Th2 cytokine ratio to the side of Thl cytokine. Therefore, RJ use in the treatment and establishing a remission of Graves' disease may be effective as a manner of antithyroid drug treatment. TSHR Ab levels of lymphocytes cell culture supernatants treated with RJ showed significantly clear decreases as concentration increases. Also, the result may suggest that RJ may exert an effect similar to an antithyroid drug for decreasing TSHR Ab levels. RJ concentration which affects both cytokin and TSHR Ab levels was found to be 400 mg/ml. It was concluded that RJ may be effective as an immunomodulatory agent in Graves' disease.