{"title":"蜂毒蜂毒®通过增加MRL/FASlpr小鼠Treg抑制皮肤病变和SLE肾炎。","authors":"Duk-Yeon Cho, Young-Mo Kang, SangHo Seol","doi":"10.1186/s42358-025-00448-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Apitoxin<sup>®</sup>, a drug based on bee venom was approved and released in Korea in 2003 as the ethical drug (ETC). It is well-known for its pain-relieving properties due to its potent anti-inflammatory effects. This raises the question of whether bee venom has benefits for other inflammatory disorders. Since its effectiveness in treating inflammation and pain associated with autoimmune diseases has been observed in several clinical cases in Korea, we conducted an efficacy study using an animal model of the systemic lupus erythematosus (SLE), an autoimmune disease with high medical unmet needs. In this research, we aim to confirm the potential therapeutic efficacy for SLE through the immunomodulation induced by bee venom.</p><p><strong>Methods: </strong>MRL/FAS<sup>lpr</sup> mice were injected subcutaneously with Apitoxin<sup>®</sup> and evaluated for clinical parameters including proteinuria, skin lesions, and lymphadenopathy, flow cytometric evaluation of regulatory T cells (Treg), quantitative evaluation of anti-dsDNA antibody in serum by ELISA, and histomorphometric analysis of kidney tissues.</p><p><strong>Results: </strong>Treatment with Apitoxin<sup>®</sup> revealed a reduction in proteinuria, skin lesions, and lymphadenopathy in MRL/FAS<sup>lpr</sup> mice. The percentage of CD3<sup>+</sup>CD4<sup>+</sup>CD25<sup>+</sup>FoxP3 (Treg) cells, which are associated with autoimmune diseases, was increased compared to the negative control (vehicle). Quantitative analysis of autoantibodies in the blood of MRL/FAS<sup>lpr</sup> mice showed a decreasing tendency in the treatment groups with Apitoxin<sup>®</sup>. Moreover, mesangial proliferation and inflammatory cell infiltration in glomeruli were significantly reduced in the treatment group with Apitoxin<sup>®</sup>, which was associated with a statistically significant decrease in the amount of IgG infiltrated into the glomeruli.</p><p><strong>Conclusion: </strong>Overall, the results confirmed that Apitoxin<sup>®</sup> induced clinical improvement in SLE by increasing the proportion of Treg cells and decreasing anti-dsDNA antibodies in the blood, which resulted in therapeutic effects on glomerulonephritis associated with decreased renal infiltration of immune complexes.</p>","PeriodicalId":48634,"journal":{"name":"Advances in Rheumatology","volume":"65 1","pages":"17"},"PeriodicalIF":2.1000,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Suppression of skin lesions and SLE nephritis by increasing Treg in MRL/FAS<sup>lpr</sup> mice by administration of bee venom Apitoxin<sup>®</sup>.\",\"authors\":\"Duk-Yeon Cho, Young-Mo Kang, SangHo Seol\",\"doi\":\"10.1186/s42358-025-00448-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Apitoxin<sup>®</sup>, a drug based on bee venom was approved and released in Korea in 2003 as the ethical drug (ETC). It is well-known for its pain-relieving properties due to its potent anti-inflammatory effects. This raises the question of whether bee venom has benefits for other inflammatory disorders. Since its effectiveness in treating inflammation and pain associated with autoimmune diseases has been observed in several clinical cases in Korea, we conducted an efficacy study using an animal model of the systemic lupus erythematosus (SLE), an autoimmune disease with high medical unmet needs. In this research, we aim to confirm the potential therapeutic efficacy for SLE through the immunomodulation induced by bee venom.</p><p><strong>Methods: </strong>MRL/FAS<sup>lpr</sup> mice were injected subcutaneously with Apitoxin<sup>®</sup> and evaluated for clinical parameters including proteinuria, skin lesions, and lymphadenopathy, flow cytometric evaluation of regulatory T cells (Treg), quantitative evaluation of anti-dsDNA antibody in serum by ELISA, and histomorphometric analysis of kidney tissues.</p><p><strong>Results: </strong>Treatment with Apitoxin<sup>®</sup> revealed a reduction in proteinuria, skin lesions, and lymphadenopathy in MRL/FAS<sup>lpr</sup> mice. The percentage of CD3<sup>+</sup>CD4<sup>+</sup>CD25<sup>+</sup>FoxP3 (Treg) cells, which are associated with autoimmune diseases, was increased compared to the negative control (vehicle). Quantitative analysis of autoantibodies in the blood of MRL/FAS<sup>lpr</sup> mice showed a decreasing tendency in the treatment groups with Apitoxin<sup>®</sup>. Moreover, mesangial proliferation and inflammatory cell infiltration in glomeruli were significantly reduced in the treatment group with Apitoxin<sup>®</sup>, which was associated with a statistically significant decrease in the amount of IgG infiltrated into the glomeruli.</p><p><strong>Conclusion: </strong>Overall, the results confirmed that Apitoxin<sup>®</sup> induced clinical improvement in SLE by increasing the proportion of Treg cells and decreasing anti-dsDNA antibodies in the blood, which resulted in therapeutic effects on glomerulonephritis associated with decreased renal infiltration of immune complexes.</p>\",\"PeriodicalId\":48634,\"journal\":{\"name\":\"Advances in Rheumatology\",\"volume\":\"65 1\",\"pages\":\"17\"},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2025-03-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Advances in Rheumatology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s42358-025-00448-5\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"RHEUMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advances in Rheumatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s42358-025-00448-5","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
Suppression of skin lesions and SLE nephritis by increasing Treg in MRL/FASlpr mice by administration of bee venom Apitoxin®.
Background: Apitoxin®, a drug based on bee venom was approved and released in Korea in 2003 as the ethical drug (ETC). It is well-known for its pain-relieving properties due to its potent anti-inflammatory effects. This raises the question of whether bee venom has benefits for other inflammatory disorders. Since its effectiveness in treating inflammation and pain associated with autoimmune diseases has been observed in several clinical cases in Korea, we conducted an efficacy study using an animal model of the systemic lupus erythematosus (SLE), an autoimmune disease with high medical unmet needs. In this research, we aim to confirm the potential therapeutic efficacy for SLE through the immunomodulation induced by bee venom.
Methods: MRL/FASlpr mice were injected subcutaneously with Apitoxin® and evaluated for clinical parameters including proteinuria, skin lesions, and lymphadenopathy, flow cytometric evaluation of regulatory T cells (Treg), quantitative evaluation of anti-dsDNA antibody in serum by ELISA, and histomorphometric analysis of kidney tissues.
Results: Treatment with Apitoxin® revealed a reduction in proteinuria, skin lesions, and lymphadenopathy in MRL/FASlpr mice. The percentage of CD3+CD4+CD25+FoxP3 (Treg) cells, which are associated with autoimmune diseases, was increased compared to the negative control (vehicle). Quantitative analysis of autoantibodies in the blood of MRL/FASlpr mice showed a decreasing tendency in the treatment groups with Apitoxin®. Moreover, mesangial proliferation and inflammatory cell infiltration in glomeruli were significantly reduced in the treatment group with Apitoxin®, which was associated with a statistically significant decrease in the amount of IgG infiltrated into the glomeruli.
Conclusion: Overall, the results confirmed that Apitoxin® induced clinical improvement in SLE by increasing the proportion of Treg cells and decreasing anti-dsDNA antibodies in the blood, which resulted in therapeutic effects on glomerulonephritis associated with decreased renal infiltration of immune complexes.
期刊介绍：
Formerly named Revista Brasileira de Reumatologia, the journal is celebrating its 60th year of publication.
Advances in Rheumatology is an international, open access journal publishing pre-clinical, translational and clinical studies on all aspects of paediatric and adult rheumatic diseases, including degenerative, inflammatory and autoimmune conditions. The journal is the official publication of the Brazilian Society of Rheumatology and welcomes original research (including systematic reviews and meta-analyses), literature reviews, guidelines and letters arising from published material.
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