{"title":"非感染性葡萄膜炎中的白细胞介素-6:生物学、实验证据和治疗策略。","authors":"","doi":"10.1016/j.bcp.2024.116605","DOIUrl":null,"url":null,"abstract":"<div><div>Uveitis is the leading cause of visual impairment worldwide. Interleukin-6 (IL-6), which is upregulated in response to inflammation, is one of the most important inflammatory cytokines associated with uveitis. Two major IL-6 receptors (IL-6R) mediate the pro-inflammatory and anti-inflammatory biological effects of IL-6. This review summarized multiple perspectives on the mechanism of IL-6-mediated uveitis, based on experimental evidence from clinical and animal models. It includes discussions on the roles of the downstream IL-6 signaling pathway, immunocytes, and the blood-retinal barrier. Therapeutic strategies aimed at blocking the action of IL-6 have progressed in clinical practice. However, due to the adverse events associated with existing biologics including infections, drugs that selectively inhibit intraocular IL-6 still require further development. The novel concept of converting the pro-inflammatory effects of IL-6 into protective effects also requires further research. In addition, the relationship between the <em>trans</em>-presentation of IL-6R and T-helper17 cells in uveitis remains unexplored. This review aims to consolidate our current understanding of the biology, signaling pathways, experimental models, and immune pathogenesis related to IL-6 and uveitis. We also discuss clinical strategies focused on blocking IL-6 as a treatment for uveitis. Targeting IL-6 provides unlimited potential for improving the diagnosis, treatment, and prognosis of uveitis.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":null,"pages":null},"PeriodicalIF":5.3000,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Interleukin-6 in non-infectious uveitis: Biology, experimental evidence and treatment strategies\",\"authors\":\"\",\"doi\":\"10.1016/j.bcp.2024.116605\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Uveitis is the leading cause of visual impairment worldwide. Interleukin-6 (IL-6), which is upregulated in response to inflammation, is one of the most important inflammatory cytokines associated with uveitis. Two major IL-6 receptors (IL-6R) mediate the pro-inflammatory and anti-inflammatory biological effects of IL-6. This review summarized multiple perspectives on the mechanism of IL-6-mediated uveitis, based on experimental evidence from clinical and animal models. It includes discussions on the roles of the downstream IL-6 signaling pathway, immunocytes, and the blood-retinal barrier. Therapeutic strategies aimed at blocking the action of IL-6 have progressed in clinical practice. However, due to the adverse events associated with existing biologics including infections, drugs that selectively inhibit intraocular IL-6 still require further development. The novel concept of converting the pro-inflammatory effects of IL-6 into protective effects also requires further research. In addition, the relationship between the <em>trans</em>-presentation of IL-6R and T-helper17 cells in uveitis remains unexplored. This review aims to consolidate our current understanding of the biology, signaling pathways, experimental models, and immune pathogenesis related to IL-6 and uveitis. We also discuss clinical strategies focused on blocking IL-6 as a treatment for uveitis. Targeting IL-6 provides unlimited potential for improving the diagnosis, treatment, and prognosis of uveitis.</div></div>\",\"PeriodicalId\":8806,\"journal\":{\"name\":\"Biochemical pharmacology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.3000,\"publicationDate\":\"2024-11-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biochemical pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0006295224006051\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochemical pharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0006295224006051","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Interleukin-6 in non-infectious uveitis: Biology, experimental evidence and treatment strategies
Uveitis is the leading cause of visual impairment worldwide. Interleukin-6 (IL-6), which is upregulated in response to inflammation, is one of the most important inflammatory cytokines associated with uveitis. Two major IL-6 receptors (IL-6R) mediate the pro-inflammatory and anti-inflammatory biological effects of IL-6. This review summarized multiple perspectives on the mechanism of IL-6-mediated uveitis, based on experimental evidence from clinical and animal models. It includes discussions on the roles of the downstream IL-6 signaling pathway, immunocytes, and the blood-retinal barrier. Therapeutic strategies aimed at blocking the action of IL-6 have progressed in clinical practice. However, due to the adverse events associated with existing biologics including infections, drugs that selectively inhibit intraocular IL-6 still require further development. The novel concept of converting the pro-inflammatory effects of IL-6 into protective effects also requires further research. In addition, the relationship between the trans-presentation of IL-6R and T-helper17 cells in uveitis remains unexplored. This review aims to consolidate our current understanding of the biology, signaling pathways, experimental models, and immune pathogenesis related to IL-6 and uveitis. We also discuss clinical strategies focused on blocking IL-6 as a treatment for uveitis. Targeting IL-6 provides unlimited potential for improving the diagnosis, treatment, and prognosis of uveitis.
期刊介绍:
Biochemical Pharmacology publishes original research findings, Commentaries and review articles related to the elucidation of cellular and tissue function(s) at the biochemical and molecular levels, the modification of cellular phenotype(s) by genetic, transcriptional/translational or drug/compound-induced modifications, as well as the pharmacodynamics and pharmacokinetics of xenobiotics and drugs, the latter including both small molecules and biologics.
The journal''s target audience includes scientists engaged in the identification and study of the mechanisms of action of xenobiotics, biologics and drugs and in the drug discovery and development process.
All areas of cellular biology and cellular, tissue/organ and whole animal pharmacology fall within the scope of the journal. Drug classes covered include anti-infectives, anti-inflammatory agents, chemotherapeutics, cardiovascular, endocrinological, immunological, metabolic, neurological and psychiatric drugs, as well as research on drug metabolism and kinetics. While medicinal chemistry is a topic of complimentary interest, manuscripts in this area must contain sufficient biological data to characterize pharmacologically the compounds reported. Submissions describing work focused predominately on chemical synthesis and molecular modeling will not be considered for review.
While particular emphasis is placed on reporting the results of molecular and biochemical studies, research involving the use of tissue and animal models of human pathophysiology and toxicology is of interest to the extent that it helps define drug mechanisms of action, safety and efficacy.