Alterations in the expression of tumor necrosis factor-alpha in the uveitis with optic nerve inflammation

N.V. Panchenko, Dr Sc (Med)

M.N. Samofalova, DM

E.N. Gonchar, DM

D.O. Prikhod’ko, DM

G.S. Arustamova, DM

A.V. Lytvyshchenko, DM

Department of Ophthalmology, Kharkiv National Medical University

Kharkiv, Ukraine

E-mail: panchenko0802@gmail.com

Purpose: To assess serum levels of tumor necrosis factor-alpha (TNF-α) in uveitis patients with optic nerve inflammation (ONI).

Materials and Methods: A retrospective evaluation of 132 patients who underwent examination and treatment for uveitis with ONI was performed. A commercially available enzyme-linked immunosorbent assay kit was used to measure serum TNF-α levels. Serum samples of 30 healthy donors were used as controls.

Results: Serum TNF-α levels in uveitis patients with ONI were 3.8 times higher compared to those in healthy controls (15.8 ± 1.02 pg/mL and 4.1 ± 1.52 pg/mL, respectively, p < 0.05). The highest increase in serum TNF-α levels compared to controls was seen in intermediate uveitis.

Conclusion: Serum TNF-α levels in active period of uveitis with ONI were found to be statistically significantly increased compared to those in controls. This finding provides the rationale for the use of anti-TNF-α agents for the treatment of uveitis with optic nerve inflammation.

Key words: uveitis with optic nerve inflammation, tumor necrosis factor-alpha



1.Molins B, Mesquida M, Lee RW, et al. Regulatory T cell levels and cytokine production in active non-infectious uveitis: in-vitro effects of pharmacological treatment. Clin Exp Immunol. 2015 Mar;179(3):529-38
Crossref   Pubmed

2.Santos Lacomba M, Marcos Martín C, Gallardo Galera JM, et al. Aqueous humor and serum tumor necrosis factor-alpha in clinical uveitis. Ophthalmic Res. 2001 Sep-Oct;33(5):251-5
Crossref   Pubmed

3.Chang KC, Shieh B, Petrash JM.  Aldose reductase mediates retinal microglia activation. Aldose reductase mediates retinal microglia activation. Biochem Biophys Res Commun. 2016 Apr 29;473(2):565-71
Crossref   Pubmed

4.Yadav UC, Shoeb M, Srivastava SK, Ramana KV. Aldose reductase deficiency protects from autoimmune- and endotoxin-induced uveitis in mice. Invest Ophthalmol Vis Sci. 2011 Oct 17;52(11):8076-85

5.Caspi RR. Understanding autoimmune uveitis through animal models. The Friedenwald Lecture. Invest Ophthalmol Vis Sci. 2011;52(3): 1872–9

6.Trinh L, Brignole-Baudouin F, Pauly A, et al. Th1- and Th2-related chemokine and chemokine receptor expression on the ocular surface in endotoxin-induced uveitis. Mol Vis. 2008; 14: 2428–34

7.Turgut B, Gul FC, Dagli F, et al. Impact of ghrelin on vitreous cytokine levels in an experimental uveitis model. Drug Des Devel Ther. 2013 9;7:19-24

8.Ortencio KP, Renzo R, Sobrinho B AA, et al. Effects of morphine on the expression of cytokines and inflammatory mediators in a rabbit model of endotoxin-induced experimental uveitis. Arq Bras Oftalmol. 2015 Nov-Dec;78(6):371-5

9.Nagata K, Maruyama K, Uno K, et al. Simultaneous analysis of multiple cytokines in the vitreous of patients with sarcoid uveitis. Invest Ophthalmol Vis Sci. 2012 Jun 20;53(7):3827-33

10.Shibata M, Sato T, Taguchi M, et al. Analysis of Cytokines Related to Helper T and Regulatory T Cells in the Vitreous of Uveitis Patients. Nippon Ganka Gakkai Zasshi. 2015 Jun;119(6):395-401

11.Chen W, Zhao B, Jiang R, et al. Cytokine expression profile in aqueous humor and sera of patients with acute anterior uveitis. Curr Mol Med. 2015 ;15(6):543-9

12.Hernández Garfella ML, Palomares Fort P, Román Ivorra J, Cervera Taulet E. Aqueous Humor Levels of Different Interleukins 1-β, 2, 6 and 10, Tumor Necrosis Factor-α and Vascular Endothelial Growth Factor in Uveitis Treated with Adalimumab. J Ophthalmic Vis Res.2015 Jan-Mar;10(1):49-54

13.Sijssens KM, Rijkers GT, Rothova A, et al. Cytokines, chemokines and soluble adhesion molecules in aqueous humor of children with uveitis. Exp Eye Res. 2007 Oct 22;85(4):443-9

14.El-Asrar AM, Struyf S, Kangave D, et al. Cytokine and CXC chemokine expression patterns in aqueous humor of patients with presumed tuberculous uveitis. Cytokine. 2012 Aug;59(2):377-81

15.El-Asrar AM, Struyf S, Kangave D, et al. Cytokine profiles in aqueous humor of patients with different clinical entities of endogenous uveitis. Clin Immunol. 2011 May;139(2):177-84

16.Lahmar I, Abou-Bacar A, Abdelrahman T, et al. Cytokine Profiles in Toxoplasmic and Viral Uveitis. J Infect Dis. 2009;199:1239-49

17.Takase H, Futagami Y, Yoshida T, et al. Cytokine Profile in Aqueous Humor and Sera of Patients with Infectious or Noninfectious Uveitis. Invest Ophthalmol Vis Sci. 2006 Apr;47(4):1557-61

18.Franks WA, Limb GA, Stanford MR, et al. Cytokines in human intraocular inflammation. Curr EyeRes. 1992; 11(Suppl):187–91

19.Foster CS, Tufail F, Waheed NK, et al. Efficacy of etanercept in preventing relapse of uveitis controlled by methotrexate. Arch Ophthalmol. 2003;121(4):437-40

20.Cordero-Coma M, Calleja S, Llorente M, et al. Serum cytokine profile in adalimumab-treated refractory uveitis patients: decreased IL-22 correlates with clinical responses. Ocul Immunol Inflamm. 2013 Jun;21(3):212-9

21.Evereklioglu C, Er H, Turkoz Y, Cekmen M. Serum levels of TNF-alpha, sIL-2R, IL-6, and IL-8 are increased and associated with elevated lipid peroxidation in patients with Behçet's disease. Mediators Inflamm. 2002 Apr;11(2):87-93

22.Mesquida M, Molins B, Llorens V, et al. Proinflammatory cytokines and C-reactive protein in uveitis associated with Behcet's disease [Electronic resource]. Mediators Inflamm. 2014. Retrieved from: http:/dx.doi.org/10.1155/2014/396204

23.Türkcü FM, Şahin A, Cingü AK, et al. Serum omentin, resistin and tumour necrosis factor-α levels in Behcet patients with and without ocular involvement. Graefes Arch Clin Exp Ophthalmol. 2015 Sep;253(9):1565-8

24.Curnow SJ, Falciani F, Durrani OM, et al. Multiplex Bead Immunoassay Analysis of Aqueous Humor Reveals Distinct Cytokine Profiles In Uveitis. Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4251-9

25.Cordero-Coma M, Sobrin L. Anti-tumor necrosis factor-α therapy in uveitis. Surv Ophthalmol. 2015 Nov-Dec;60(6):575-89

26.Jaffe GL, Thorne JE, Scales D, et al. SAT0523 Adalimumab in Patients with Active, Non-Infectious Uveitis Requiring High-Dose Corticosteroids: the Visual-1 Trial. Ann Rheum Dis. 2015;74:849-50

27.Brooks M. FDA Clears Adalimumab (Humira) for Uveitis [Electronic resource] / M. Brooks // Medscape. – 2016. – Retrieved from: http://www.medscape.com/viewarticle/865654

28.Khovalyg NM, Fadeeva NI, Korenovskiy YuV. [Determination of matrix metalloproteinase type 9 in the plasma of premature neonates for the prognosis of perinatal damage to the CNS of premature neonates]. In: [Proceedings of the 8th International Congress on Health and Education in the 21st Century: Concepts of Diseases of Civilization]. Health and Education in the 21st Century Journal. 2007;9(4):334. Russian

29.Yamada H, Yoneda M, Inaguma S, et al. Infliximab counteracts tumor necrosis factor-α-enhanced induction of matrix metalloproteinases that degrade claudin and occludin in non-pigmented ciliary epithelium. Biochem Pharmacol. 2013 Jun 15;85(12):1770-82

30.Panchenko NV, Samofalova MN, Friantseva MV. [Levels of matrix metalloproteinase type 9 in different outcomes of uveitis with optic nerve inflammation]. Oftalmologiia. Vostochnaia Evropa. 2016;6(2):210-6. Russian