IL-6 antagonizes TGF-beta and abolishes immune privilege in eyes with endotoxin-induced uveitis
- PMID: 10937571
IL-6 antagonizes TGF-beta and abolishes immune privilege in eyes with endotoxin-induced uveitis
Abstract
Purpose: To determine the immunosuppressive status of aqueous humor (AqH) from mouse eyes afflicted with endotoxin-induced uveitis (EIU) and to identify the relevant cytokines responsible for immunomodulatory activity within EIU AqH.
Methods: Bacterial lipopolysaccharide (LPS) was injected into hind footpads of C3H/HeN mice; and AqH, collected at 6, 12, 24, and 48 hours, was evaluated for content of transforming growth factor (TGF)-beta, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and interferon (IFN)-gamma and capacity to suppress anti-CD3-driven T-cell proliferation. Cytokine mRNA expression in iris-ciliary body (I/CB) was analyzed by RNase protection assays.
Results: During 6 to 24 hours after LPS injection, total TGF-beta levels in AqH increased even though the fluid lost its capacity to suppress T-cell activation. At this time, AqH contained high levels of IL-6, and I/CB contained high levels of IL-6 mRNA. When IL-6 was neutralized with specific antibodies, inflamed AqH reacquired its capacity to suppress T-cell activation, which correlated with high levels of TGF-beta. Coinjection of IL-6 plus antigen into the anterior chamber of the eye of normal mice prevented antigen-specific anterior chamber-associated immune deviation (ACAID).
Conclusions: LPS-induced intraocular inflammation is associated with local production of IL-6, which robs AqH of its immunosuppressive activity, perhaps by antagonizing TGF-beta. The fact that IL-6 antagonized ACAID induction in normal eyes suggests that strategies to suppress the intraocular synthesis of IL-6 may reduce inflammation and restore ocular immune privilege.
Similar articles
-
Effects of experimental ocular inflammation on ocular immune privilege.Invest Ophthalmol Vis Sci. 1999 Aug;40(9):2010-8. Invest Ophthalmol Vis Sci. 1999. PMID: 10440255
-
Analysis of immune privilege in eyes with Mycobacteria tuberculosa adjuvant-induced uveitis.Ocul Immunol Inflamm. 2005 Apr-Jun;13(2-3):139-47. doi: 10.1080/09273940490912489. Ocul Immunol Inflamm. 2005. PMID: 16019673
-
Analysis of immunomodulatory activities of aqueous humor from eyes of mice with experimental autoimmune uveitis.J Immunol. 2000 Feb 1;164(3):1185-92. doi: 10.4049/jimmunol.164.3.1185. J Immunol. 2000. PMID: 10640729
-
Ocular immune privilege and the impact of intraocular inflammation.DNA Cell Biol. 2002 May-Jun;21(5-6):453-9. doi: 10.1089/10445490260099746. DNA Cell Biol. 2002. PMID: 12167248 Review.
-
[Immunologic responses of the anterior chamber of the eye].Allergol Immunopathol (Madr). 1994 Jan-Feb;22(1):23-7. Allergol Immunopathol (Madr). 1994. PMID: 8030580 Review. Spanish.
Cited by
-
Growth factor restriction impedes progression of wound healing following cataract surgery: identification of VEGF as a putative therapeutic target.Sci Rep. 2016 Apr 14;6:24453. doi: 10.1038/srep24453. Sci Rep. 2016. PMID: 27076230 Free PMC article.
-
Repurposing an orally available drug for the treatment of geographic atrophy.Mol Vis. 2016 Apr 2;22:294-310. eCollection 2016. Mol Vis. 2016. PMID: 27110092 Free PMC article.
-
Nanomicelle-Assisted Targeted Ocular Delivery with Enhanced Antiinflammatory Efficacy In Vivo.Adv Sci (Weinh). 2017 Nov 10;5(1):1700455. doi: 10.1002/advs.201700455. eCollection 2018 Jan. Adv Sci (Weinh). 2017. PMID: 29375972 Free PMC article.
-
The lens as a model for fibrotic disease.Philos Trans R Soc Lond B Biol Sci. 2011 Apr 27;366(1568):1301-19. doi: 10.1098/rstb.2010.0341. Philos Trans R Soc Lond B Biol Sci. 2011. PMID: 21402588 Free PMC article. Review.
-
Advancements in Understanding Immunogenicity of Biotherapeutics in the Intraocular Space.AAPS J. 2017 Nov;19(6):1656-1668. doi: 10.1208/s12248-017-0128-y. Epub 2017 Aug 9. AAPS J. 2017. PMID: 28795351 Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
