Cytokines in uveitis

Weinstein, Jessica E.; Pepple, Kathryn L.

doi:10.1097/icu.0000000000000466

Cited by 91 publications

(78 citation statements)

References 121 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Figure shows a proposed pathogenic mechanism of uveitis and the potential targets of biological therapies. The hypothesis shown suggests the primary involvement of pro‐inflammatory cytokines in ocular inflammation, including interleukins (ILs), interferons, and tumour necrosis factor alpha (TNF‐α) . A pivotal study found significantly higher levels of cytokines in the aqueous humour of uveitis patients than controls, including IL‐6, IL‐10, IL‐17, IL‐22, IL‐23, interferon‐γ and TNF‐α .…”

Section: Pathophysiologymentioning

confidence: 99%

“…The hypothesis shown suggests the primary involvement of pro-inflammatory cytokines in ocular inflammation, including interleukins (ILs), interferons, and tumour necrosis factor alpha (TNF-α). [16][17][18] A pivotal study found significantly higher levels of cytokines in the aqueous humour of uveitis patients than controls, including IL-6, IL-10, IL-17, IL-22, IL-23, interferon-γ and TNF-α. 19 Hence, targeted cytokine therapy was trialled, including anti-TNF-α agents initially developed to inhibit the same pro-inflammatory cytokines identified in systemic rheumatic diseases.…”

Section: Pathophysiologymentioning

confidence: 99%

See 1 more Smart Citation

The use of biologic agents in the management of uveitis

Trivedi

Katelaris

2019

Internal Medicine Journal

View full text Add to dashboard Cite

The uveitides are a heterogenous group of ocular inflammatory disorders that account for the third highest cause of blindness worldwide, responsible for 5–10% of visual impairment globally. Up to 35% of patients with uveitis can suffer significant vision loss. To prevent irreversible structural damage and blindness, it is important that the diagnosis and commencement of appropriate therapy occurs promptly. Management includes topical and systemic corticosteroid therapy and conventional immunomodulatory agents, including methotrexate, azathioprine, mycophenolate mofetil and cyclosporin. Significant progress has been made in the past decade in our understanding of the immunopathological pathways that drive intraocular inflammation, allowing the development of targeted therapy with biologic agents. These include TNF‐α inhibitors, such as infliximab, adalimumab and etanercept; interleukin blockers, such as tocilizumab and daclizumab; and other targeted therapies, such as rituximab and abatacept. The efficacy of these agents has been studied in cases of severe uveitis that are refractory to conventional immunomodulatory agents and provide exciting results that have revolutionised uveitis management. Though the biologic era has provided a large armamentarium to treat uveitis, ongoing challenges and cases of recalcitrant uveitis remain, posing a challenge to internal medicine physicians. This comprehensive review aims to construct an updated summary on the existing evidence pertaining to the use of biologic agents in the treatment of uveitis. Methods include a systematic search for studies between 2000 and 2018 using PubMed, EMBASE, Ovid MEDLINE and Cochrane libraries.

show abstract

Section: Pathophysiologymentioning

confidence: 99%

Section: Pathophysiologymentioning

confidence: 99%

The use of biologic agents in the management of uveitis

Trivedi

Katelaris

2019

Internal Medicine Journal

View full text Add to dashboard Cite

show abstract

“…TNF and IL-17A have been shown to disrupt blood-brain barrier (BBB) by destabilizing tight junctions (42). We showed that IFN-C was able to prevent the disruption of ZO-1 distribution on ARPE-19 cells and consequently to counteract the reduction of transepithelial electrical resistance (Figures 4 and 5).…”

Section: Suppression Of Nf-kb Leads To the Downregulation Of Inflammamentioning

confidence: 88%

“…ARPE-19 cells were grown in 8 well microscopic slides for 4 weeks in low serum media until they differentiated and acquired a cobblestone appearance similar to primary RPE cells. During uveitis, elevated levels of cytokines such as TNF or IL-17A cause disruption of RPE barrier properties (36,42). These were added to differentiated ARPE-19 cells for 48 hr at 50 ng/ml each.…”

Section: Protection Against Disruption Of Barrier Properties Of Arpe-mentioning

confidence: 99%

A Cell Penetrating Peptide from Type I Interferon Protects the Retina in a Mouse Model of Autoimmune Uveitis

Ahmed

et al. 2019

Preprint

View full text Add to dashboard Cite

Experimental autoimmune uveitis (EAU) in rodents recapitulates many features of the disease in humans and has served as a useful tool for the development of therapeutics. A peptide from C-terminus of interferon 1, conjugated to palmitoyl-lysine for cell penetration, denoted as IFN-C, was tested for its anti-inflammatory properties in ARPE-19 cells, followed by testing in a mouse model of EAU. Treatment with IFN-C and evaluation by RT-qPCR showed the induction of anti-inflammatory cytokines and chemokine. Inflammatory markers induced by treatment with TNF were suppressed when IFN-C was simultaneously present. TNF- mediated induction of NF-kB and signaling by IL-17A were attenuated by IFN-C.Differentiated ARPE-19 cells were treated with TNF in the presence or absence IFN-C and analyzed by immmunhistochemistry. IFN-C protected against the disruption integrity of tight junction proteins. Similarly, loss of transepithelial resistance caused by TNF was prevented by IFN-C. B10.RIII mice were immunized with a peptide from interphotoreceptor binding protein (IRBP) and treated by gavage with IFN-C. Development of uveitis was monitored by histology, fundoscopy, SD-OCT, and ERG. Treatment with IFN-C prevented uveitis in mice immunized with the IRBP peptide. Splenocytes isolated from mice with ongoing EAU exhibited antigenspecific T cell proliferation that was inhibited in the presence of IFN-C. IFN-C peptide exhibits anti-inflammatory properties and protects mice against damage to retinal structure and function suggesting that it has therapeutic potential for the treatment of autoimmune uveitis.

show abstract

“…It is well known that cytokines play an important role in the pathogenesis of uveitis. 52 We therefore investigated whether the different genotypes of rs3829794 affected these cytokines, such as IFNc, IL-10, IL-17, IL-8, IL-6, MCP-1, IL-1b, and TNF-a. Unexpectedly, we found an increased production of IL-10 in the CC genotype, which is different from its stimulatory effect on other cytokines.…”

Section: Discussionmentioning

confidence: 99%

Replication of Genome-Wide Association Analysis Identifies New Susceptibility Loci at Long Noncoding RNA Regions for Vogt-Koyanagi-Harada Disease

Deng

et al. 2019

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

Citation: Qi J, Du L, Deng J, et al. Replication of genome-wide association analysis identifies new susceptibility loci at long noncoding RNA regions for Vogt-Koyanagi-Harada disease. Invest Ophthalmol Vis Sci. 2019;60:4820-4829. https://doi.org/ 10.1167/iovs.19-27708PURPOSE. This study was aimed at investigating the association of long noncoding RNA (lncRNA)-related single nucleotide polymorphisms (SNPs) with Vogt-Koyanagi-Harada (VKH) disease. METHODS.LncRNA-related SNPs were selected by multi-omics analysis. Genotyping, expression of lncRNA and mRNA, cell proliferation, and cytokine production were tested by MassARRAY System, real-time PCR, CCK8, and ELISA. RESULTS.A significant association with VKH was found for lnc-TOR3A-1:1/rs3829794, which is located in a non-HLA region (CC genotype: Bonferroni corrected P values [P C ] ¼ 2.98 3 10 À8 , odds ratio [OR] ¼ 0.62; TT genotype: P C ¼ 1.64 3 10 À8 , OR ¼ 1.57; C allele: P C ¼ 1.39 3 10 À12 , OR ¼ 0.71). Additionally, an association was found for four lncRNA SNPs located in the HLA region. Functional experiments in rs3829794 genotyped individuals showed decreased ABL2 (ABL proto-oncogene 2, nonreceptor tyrosine kinase) expression, decreased proliferation of anti-CD3 plus anti-CD28-stimulated peripheral blood mononuclear cells (PBMCs), and an increased production of IL-10 in CC carriers compared to TT carriers (P ¼ 0.0073, P ¼ 0.0011, and P ¼ 0.002, respectively). CONCLUSIONS.Our study identified five new loci associated with VKH susceptibility and identified a functional variant (lnc-TOR3A-1:1/rs3829794) that confers risk for VKH, which is possibly mediated by modulating gene expression, proliferation of lymphocytes, and regulation of anti-inflammatory cytokine production.

show abstract

Cytokines in uveitis

Abstract: Th17 cells, and their related cytokines, are important inflammatory mediators in autoimmune uveitis. Animal and human studies continue to provide new information to direct development of new cytokine-targeted therapies for patients with uveitis.

Cited by 91 publications

References 121 publications

The use of biologic agents in the management of uveitis

The use of biologic agents in the management of uveitis

A Cell Penetrating Peptide from Type I Interferon Protects the Retina in a Mouse Model of Autoimmune Uveitis

Replication of Genome-Wide Association Analysis Identifies New Susceptibility Loci at Long Noncoding RNA Regions for Vogt-Koyanagi-Harada Disease

Contact Info

Product

Resources

About