Serum Cytokine Receptor Levels in Noninfectious UveitisTorun N.a · Callizo J.a, b · Orlic N.a · Scherer M.a · Hartmann C.a · Pleyer U.a
aCharité, University School of Medicine Berlin, Campus Virchow Klinikum, Clinic of Ophthalmology, Berlin, Germany; bUniversidad Autónoma de Barcelona, Barcelona, Spain
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Purpose: Understanding of the role of cytokines in uveitis may provide new clues to its treatment. Therefore, the purpose of our study was to evaluate systemic cytokine receptor expression in patients with noninfectious uveitis. Method: Serum concentrations of soluble interleukin-2 receptor α (IL-2 s Rα) and soluble tumor necrosis factor receptor-1 (sTNF-R1) were measured in patients with intermediate uveitis (n = 26), posterior uveitis (n = 23) and healthy controls (n = 12) using ELISA. All patients were identified in a consecutive series of 996 uveitis patients who had been diagnosed between 1998 and 2002 and classified according to the recommendations of the International Uveitis Study Group. Inclusion criteria were idiopathic, active intraocular inflammation, uveitis as a primary process and no systemic anti-inflammatory treatment at the time of blood sampling. None of the patients had an underlying systemic disease. Results: Serum concentrations of IL-2 s Rα were significantly increased in patients with posterior (p < 0.005) and intermediate uveitis (p < 0.005) as compared to healthy controls. Similarly, concentrations of sTNF-R1 appeared to be increased in posterior (p < 0.005) and intermediate (p < 0.005) uveitis patients when compared to controls. Conclusions: Our results may suggest that patients with noninfectious uveitis express systemic cytokine receptors such as TNF-R1 and IL-2 Rα, which may have an important role in the immune response of the eye and may lead to new immunomodulatory approaches.
© 2005 S. Karger AG, Basel
- Nussenblatt RB: The natural history of uveitis. Int Ophthalmol 1990;14:303–308.
- Vincenti F, Kirkman R, Light S, Bumgardner G, Pescovitz M, Halloran P, Neylan J, Wilkinson A, Ekberg H, Gaston R, Backman L, Burdick J: Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation. N Engl J Med 1998;338:161–165.
- Gorman JD, Sack KE, Davis JC Jr: Treatment of ankylosing spondylitis by inhibition of tumor necrosis factor alpha. N Engl J Med 2002;346:1349–1356.
- Murphy CC, Greiner K, Plskova J, Duncan L, Frost A, Isaacs JD, Rebello P, Waldmann H, Hale G, Forrester JV, Dick AD: Neutralizing tumor necrosis factor activity leads to remission in patients with refractory noninfectious posterior uveitis. Arch Ophthalmol 2004;122:845–851.
- de Vos AF, van Haren MA, Verhagen C, Hoekzema R, Kijlstra A: Kinetics of intraocular tumor necrosis factor and interleukin-6 in endotoxin-induced uveitis in the rat. Invest Ophthalmol Vis Sci 1994;35:1100–1106.
- Caspi RR: Th1 and Th2 response in pathogenesis and regulation of experimental autoimmune uveoretinitis. Int Rev Immunol 2002;21:197–208.
- Waldmann AT: The IL-2/IL-2 receptor system: A target for rational immune intervention. Immunol Today 1993;14:264–270.
- Wolf RE, Brelsford WG, Hall VC, Adams SB: Cytokines and soluble interleukin 2 receptors in rheumatoid arthritis. J Rheumatol 1992;19:524–528.
- Bloch-Michel E, Nussenblatt RB: International Uveitis Study Group recommendations for the evaluation of intraocular inflammatory disease. Am J Ophthalmol 1987;103:234–235.
- Tracey KJ, Cerami A: Tumor necrosis factor: A pleiotropic cytokine and therapeutic target. Annu Rev Med 1994;45:491–503.
- Nakamura S, Yamakawa T, Sugita M, Kijima M, Ishioka M, Tanaka S, Ohno S: The role of tumor necrosis factor-alpha in the induction of experimental autoimmune uveoretinitis in mice. Invest Ophthalmol Vis Sci 1994;35:3884–3889.
- Foxman EF, Zhang M, Hurst SD, Muchamuel T, Shen D, Wawrousek EF, Chan CC, Gery I: Inflammatory mediators in uveitis: Differential induction of cytokines and chemokines in Th1- versus Th2-mediated ocular inflammation. J Immunol 2002;168:2483–2492.
- Fleisher LN, Ferrell JB, McGahan MC: Ocular inflammatory effects of intravitreally injected tumor necrosis factor-alpha and endotoxin. Inflammation 1990;14:325–335.
- Ferguson TA, Herndon JM, Dube P: The immune response and the eye: A role for TNF alpha in anterior chamber-associated immune deviation. Invest Ophthalmol Vis Sci 1994;35:2643–2651.
- Santos Lacomba M, Marcos Martin C, Gallardo Galera JM, Gomez Vidal MA, Collantes Estevez E, Ramirez Chamond R, Omar M: Aqueous humor and serum tumor necrosis factor-alpha in clinical uveitis. Ophthalmic Res 2001;33:251–255.
- Franks WA, Limb GA, Stanford MR, Ogilvie J, Wolstencroft RA, Chignell AH, Dumonde DC: Cytokines in human intraocular inflammation. Curr Eye Res 1992;11(suppl):187–191.
- Lantz M, Malik S, Slevin ML, Olsson I: Infusion of tumor necrosis factor (TNF) causes an increase in circulating TNF-binding protein in humans. Cytokine 1990;2:402–406.
- Chouaib S, Branellec D, Buurman WA: More insights into the complex physiology of TNF. Immunol Today 1991;12:141–142.
- Andus T, Gross V, Holstege A, Ott M, Weber M, David M, Gallati H, Gerok W, Schölmerich J: High concentrations of soluble tumor necrosis factor receptors in ascites. Hepatology 1992;16:749–755.
- Turan B, Gallati H, Erdi H, Gurler A, Michel BA, Villiger PM: Systemic levels of the T cell regulatory cytokines IL-10 and IL-12 in Behçet’s disease: Soluble TNFR-75 as a biological marker of disease activity. J Rheumatol 1997;24:128–132.
- Greiner K, Murphy CC, Willermain F, Duncan L, Plskova J, Hale G, Isaacs JD, Forrester JV, Dick AD: Anti TNF-α therapy modulates the phenotype of peripheral blood CD4+ T cells in patients with posterior segment intraocular inflammation. Invest Ophthalmol Vis Sci 2004;45:170–176.
- Aderka D, Engelmann H, Maor Y, Brakebusch C, Wallach D: Stabilization of the bioactivity of tumor necrosis factor by its soluble receptors. J Exp Med 1992;175:323–329.
- Rubin LA, Kurman CC, Fritz ME, Biddison WE, Boutin B, Yarchoan R, Nelson DL: Soluble interleukin 2 receptors are released from activated human lymphoid cells in vitro. J Immunol 1985;135:3172–3177.
- Taniguchi T, Minami Y: The IL-2/IL-2 receptor system: A current overview. Cell 1993;73:5–8.
- Arocker-Mettinger E, Asenbauer T, Ulbrich S, Grabner G: Serum interleukin 2-receptor levels in uveitis. Curr Eye Res 1990;9:25–29.
- BenEzra D, Maftzir G, Kalichman I, Barak V: Serum levels of interleukin-2 receptor in ocular Behçet’s disease. Am J Ophthalmol 1993;115:26–30.
- Martin CM, Lacomba MS, Molina CIS, Chamond RR, Galera JM, Estevez EC: Levels of soluble ICAM-1 and soluble IL-2R in the serum and aqueous humor of uveitis patients. Curr Eye Res 2000;20:287–292.
- Nussenblatt RB, Thompson DJ, Li Z, Peterson JS, Robinson RR, Shames RS, Nagarajan S, Tang MT, Mailman M, Velez G, Roy C, Levy-Clarke GA, Suhler EB, Djalilian A, Sen HN, Al-Khatib S, Ursea R, Srivastava S, Bamji A, Mellow S, Sran P, Waldmann TA, Buggage RR: Humanized anti-interleukin-2 (IL-2) receptor alpha therapy: Long-term results in uveitis patients and preliminary safety and activity data for establishing parameters for subcutaneous administration. J Autoimmun 2003;21:283–293.
- Joseph A, Raj D, Dua HS, Powell PT, Lanyon PC, Powell RJ: Infliximab in the treatment of refractory posterior uveitis. Ophthalmology 2003;110:1449–1453.
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