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PLOS ONE  2014 

An Anti-Interleukin-2 Receptor Drug Attenuates T- Helper 1 Lymphocytes-Mediated Inflammation in an Acute Model of Endotoxin-Induced Uveitis

DOI: 10.1371/journal.pone.0090216

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Abstract:

The aim of the present study was to evaluate the anti-inflammatory efficacy of Daclizumab, an anti-interleukin-2 receptor drug, in an experimental uveitis model upon a subcutaneous injection of lipopolysaccharide into Lewis rats, a valuable model for ocular acute inflammatory processes. The integrity of the blood-aqueous barrier was assessed 24 h after endotoxin-induced uveitis by evaluating two parameters: cell count and protein concentration in aqueous humors. The histopathology of all the ocular structures (cornea, lens, sclera, choroid, retina, uvea, and anterior and posterior chambers) was also considered. Enzyme-linked immunosorbent assays of the aqueous humor samples were performed to quantify the levels of the different chemokine and cytokine proteins. Similarly, a biochemical analysis of oxidative stress-related markers was also assessed. The inflammation observed in the anterior chamber of the eyes when Daclizumab was administered with endotoxin was largely prevented since the aqueous humor protein concentration substantially lowered concomitantly with a significant reduction in the uveal and vitreous histopathological grading. Th1 lymphocytes-related cytokines, such as Interleukin-2 and Interferon-γ, also significantly reduced with related anti-oxidant systems recovery. Daclizumab treatment in endotoxin-induced uveitis reduced Th1 lymphocytes-related cytokines, such as Interleukin-2 and Interferon gamma, by about 60–70% and presented a preventive role in endotoxin-induced oxidative stress. This antioxidant protective effect of Daclizumab may be related to several of the observed Daclizumab effects in our study, including IL-6 cytokine regulatory properties and a substantial concomitant drop in INFγ. Concurrently, Daclizumab treatment triggered a significant reduction in both the uveal histopathological grading and protein concentration in aqueous humors, but not in cellular infiltration.

References

[1]  Trinh L, Brignole-Baudouin F, Pauly A, Liang H, Houssier M, et al. (2008) Th1- and Th2-related chemokine and chemokine receptor expression on the ocular surface in endotoxin-induced uveitis. Mol Vis 14: 2428–2434.
[2]  Chang JH, McCluskey PJ, Wakefield D (2005) Acute anterior uveitis and HLA-B27. Surv Ophthalmol 50: 364–88. doi: 10.1016/j.survophthal.2005.04.003
[3]  Sijssens KM, Rijkers GT, Rothova A, Stilma JS, Schellekens PA, et al. (2007) Cytokines, chemokines and soluble adhesion molecules in aqueous humor of children with uveitis. Exp Eye Res 85: 443–449. doi: 10.1016/j.exer.2007.06.011
[4]  Caspi RR (2006) Animal models of autoimmune and immune-mediated uveitis. Drug Discovery Today: Disease Models 3: 3–9. doi: 10.1016/j.ddmod.2006.03.005
[5]  Rosenbaum JT, McDevitt HO, Guss RB, Egbert PR (1980) Endotoxin-induced uveitis in rats as a model for human disease. Nature 286: 611–613. doi: 10.1038/286611a0
[6]  Smith JR, Hart PH, Williams KA (1998) Basic pathogenic mechanisms operating in experimental models of acute anterior uveitis. Immunol Cell Biol 76: 497–512. doi: 10.1046/j.1440-1711.1998.00783.x
[7]  Chen W, Hu X, Zhao L, Li S, Lu H (2009) Expression of toll-like receptor 4 in uvea-resident tissue macrophages during endotoxin-induced uveitis. Mol Vis 15: 619–628.
[8]  Guha M, Mackman N (2001) LPS induction of gene expression in human monocytes. Cell Signal 13: 85–94. doi: 10.1016/s0898-6568(00)00149-2
[9]  Xu Y, Chen W, Lu H, Hu X, Li S, et al. (2010) The expression of cytokines in the aqueous humor and serum during endotoxin-induced uveitis in C3H/HeN mice. Mol Vis 16: 1689–1695.
[10]  Foxman EF, Zhang M, Hurst SD, Muchamuel T, Shen D, et al. (2002) Inflammatory mediators in uveitis: differential induction of cytokines and chemokines in Th1- versus Th2-mediated ocular inflammation. J Immunol 168: 2483–2492. doi: 10.4049/jimmunol.168.5.2483
[11]  Ooi KG, Galatowicz G, Calder VL, Lightman SL (2006) Cytokines and chemokines in uveitis: is there a correlation with clinical phenotype? Clin Med Res 4: 294–309. doi: 10.3121/cmr.4.4.294
[12]  Herbort CP, Okumura A, Mochizuki M (1988) Endotoxin-induced uveitis in the rat. A study of the role of inflammation mediators. Graefes Arch Clin Exp Ophthalmol 226: 553–558. doi: 10.1007/bf02169204
[13]  Zhang WJ, Wei H, Hagen T, Frei B (2007) Alpha-lipoic acid attenuates LPS-induced inflammatory responses by activating the phosphoinositide 3-kinase/Aktsignaling pathway. PNAS 104: 4077–4082. doi: 10.1073/pnas.0700305104
[14]  Wuest SC, Edwan J, Martin JF, Han S, Perry JSA, et al. (2011) A vital role for IL-2 trans-presentation in DC-mediated T cell activation in humans as revealed by daclizumab therapy. Nat Med 17: 604–609. doi: 10.1038/nm.2365
[15]  Busse D, de la Rosa M, Hobiger K, Thurley K, Flossdorf M, et al. (2010) Competing feedback loops shape IL-2 signaling between helper and regulatory T lymphocytes in cellular microenvironments. PNAS 107: 3058–3063. doi: 10.1073/pnas.0812851107
[16]  Nussenblatt RB, Fortin E, Schiffman R, Rizzo L, Smith J, et al. (1999) Treatment of noninfectious intermediate and posterior uveitis with the humanized anti-Tac mAb: a phase I/II clinical trial. PNAS 96: 7462–7466. doi: 10.1073/pnas.96.13.7462
[17]  Heiligenhaus A, Thurau S, Hennig M, Grajewski RS, Wildner G (2010) Anti-inflammatory treatment of uveitis with biologicals: new treatment options that reflect pathogenetic knowledge of the disease. Graefes Arch Clin Exp Ophthalmol 248: 1531–1551. doi: 10.1007/s00417-010-1485-8
[18]  Yeh S, Wroblewski K, Buggage R, Li Z, Kurup SK, et al. (2008) High-dose humanized anti-IL-2 receptor alpha antibody (daclizumab) for the treatment of active, non-infectious uveitis. J Autoimmun 31: 91–97. doi: 10.1016/j.jaut.2008.05.001
[19]  Nussenblatt R B, Peterson JS, Foster CS, Rao NA, See RF, et al. (2005) Initial evaluation of subcutaneous daclizumab treatments for noninfectious uveitis: a multicenter noncomparative interventional case series. Ophthalmology 112: 764–770. doi: 10.1016/j.ophtha.2004.12.034
[20]  Sen HN, Levy-Clarke G, Faia LJ, Li Z, Yeh S, et al. (2009) High-dose Daclizumab for the Treatment of Juvenile Idiopathic Arthritis–Associated Active Anterior Uveitis. Am J Ophthalmol 148: 696–703. doi: 10.1016/j.ajo.2009.06.003
[21]  Vincenti F, Kirkman R, Light S, Bumgardner G, Pescovitz M, et al. (1998) Interleukin-2–receptor blockade with daclizumab to prevent acute rejection in renal transplantation. N Engl J Med 338: 161–165. doi: 10.1056/nejm199801153380304
[22]  Mullen JC, Oreopoulos A, Lien DC, Bentley MJ, Modry DL, et al. (2007) A randomized, controlled trial of daclizumab vs anti-thymocyte globulin induction for lung transplantation. J Heart Lung Transplant 26: 504–510. doi: 10.1016/j.healun.2007.01.032
[23]  Sutherland DE, Gruessner RW, Dunn DL, Matas AJ, Humar A, et al. (2001) Lessons learned from more than 1,000 pancreas transplants at a single institution. Ann Surg 233: 463–501. doi: 10.1097/00000658-200104000-00003
[24]  Rech AJ, Vonderheide RH (2009) Clinical use of anti-CD25 antibody daclizumab to enhance immune responses to tumor antigen vaccination by targeting regulatory T cells. Ann NY Acad Sci 1174: 99–106. doi: 10.1111/j.1749-6632.2009.04939.x
[25]  Bousquet E, Zhao M, Ly A, Leroux Les Jardins G, Goldenberg B, et al.. (2012) The aldosterone-mineralocorticoid receptor pathway exerts anti-inflammatory effects in endotoxin-induced uveitis. PLoS One 7 (11).
[26]  Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275.
[27]  Peterson GL (1977) A simplification of the protein assay method of Lowry, et al. which is more generally applicable. Anal Biochem 83: 346–356. doi: 10.1016/0003-2697(77)90043-4
[28]  Richard MJ, Guiraud P, Meo J, Favier A (1992) High performance liquid chromatography separation of malondialdehyde-thiobarbituric acid adduct in biological materials (plasma and human cell) using a commercially available reagent. J Chromatogr 577: 9–18. doi: 10.1016/0378-4347(92)80593-f
[29]  Romero MJ, Bosch-Morell F, Romero B, Rodrigo JM, Serra MA, et al. (1998) Serum malondialdehyde: possible use for the clinical management of chronic hepatitis C patients. Free Radical Biol Med 25: 993–997. doi: 10.1016/s0891-5849(98)00118-x
[30]  Reed DJ, Babson JR, Beatty PW, Brodie AE, Ellis WW, et al. (1980) High-performance liquid chromatography analysis of nanomole levels of glutathione, glutathione disulfide, and related disulfides. Anal Biochem 106: 55–62. doi: 10.1016/0003-2697(80)90118-9
[31]  Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70: 158–169.
[32]  Ilieva I, Ohgami K, Shiratori K, Koyama Y, Yoshida K, et al. (2004) The effects of Ginkgo biloba extract on lipopolysaccharide-induced inflammation in vitro and in vivo. Exp Eye Res 79: 181–187. doi: 10.1016/j.exer.2004.03.009
[33]  Steinke JW, Borish L (2006) Cytokines and chemokines. J Allergy Clin Immunol 117: S441–S445. doi: 10.1016/j.jaci.2005.07.001
[34]  De Vos AF, Klaren VN, Kijlstra A (1994) Expression of multiple cytokines and IL-1RA in the uvea and retina during endotoxin-induced uveitis in the rat. Invest Ophthalmol Vis Sci 35: 3873–3883.
[35]  Mérida S, Sancho-Tello M, Muriach M, Miranda M, Navea A, et al. (2013) Lipoic acid lessens Th1-mediated inflammation in lipopolysaccharide-induced uveitis reducing selectively Th1 lymphocytes-related cytokines release. Free Rad Res 47: 593–601. doi: 10.3109/10715762.2013.805882
[36]  Reem GH, Yeh NH (1984) Interleukin 2 regulates expression of its receptor and synthesis of gamma interferon by human T lymphocytes. Science 225: 429–430. doi: 10.1126/science.6429853
[37]  Bird JJ, Brown DR, Mullen AC, Moskowitz NH, Mahowald MA, et al. (1998) Helper T cell differentiation is controlled by the cell cycle. Immunity 9: 229–237. doi: 10.1016/s1074-7613(00)80605-6
[38]  McDyer JF, Li Z, John S, Yu X, Wu CY, et al. (2002) IL-2 receptor blockade inhibits late, but not early, IFN-gamma and CD40 ligand expression in human T cells: disruption of both IL-12-dependent and -independent pathways of IFN-gamma production. J Immunol 169: 2736–2746. doi: 10.4049/jimmunol.169.5.2736
[39]  Snyder JT, Shen J, Azmi H, Hou J, Fowler DH, et al. (2007) Direct inhibition of CD40L expression can contribute to the clinical efficacy of daclizumab independently of its effects on cell division and Th1/Th2 cytokine production. Blood 109: 5399–5406. doi: 10.1182/blood-2006-12-062943
[40]  Banchereau J, Pascual V, O'Garra A (2012) From IL-2 to IL-37: the expanding spectrum of anti-inflammatory cytokines. Nat Immunol 13: 925–931. doi: 10.1038/ni.2406
[41]  Hollyfield JG, Bonilha VL, Rayborn ME, Yang X, Shadrach KG (2008) Oxidative damage-induced inflammation initiates age-related macular degeneration. Nat Med 14: 194–198. doi: 10.1038/nm1709
[42]  Rao NA, Wu GS (2000) Free radical mediated photoreceptor damage in uveitis. Prog Retin Eye Res 19: 41–68. doi: 10.1016/s1350-9462(99)00003-8
[43]  Lambeth JD (2004) NOX enzymes and the biology of reactive oxygen. Nat Rev Immunol 4: 181–189. doi: 10.1038/nri1312
[44]  Bosch-Morell F, Flohé L, Marín N, Romero FJ (1999) 4-hidroxynonenal inhibits gluthatione peroxidase: protection by glutathione. Free Radical Biol Med 26: 1383–1387. doi: 10.1016/s0891-5849(98)00335-9
[45]  Bosch-Morell F, Roma J, Marin N, Romero B, Rodríguez-Galietero A, et al. (2002) Role of oxygen and nitrogen species in experimental uveitis: anti-inflammatory activity of the synthetic antioxidant ebselen. Free Radical Biol Med 33: 669–675. doi: 10.1016/s0891-5849(02)00954-1
[46]  Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S (2011) The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta 1813: 878–888. doi: 10.1016/j.bbamcr.2011.01.034
[47]  Kaplanski G, Marin V, Montero-Julian F, Mantovani A, Farnarier C (2003) IL-6: a regulator of the transition from neutrophil to monocyte recruitment during inflammation. Trends Immunol 24: 25–29. doi: 10.1016/s1471-4906(02)00013-3
[48]  Wruck CJ, Streetz K, Pavic G, G?tz ME, Tohidnezhad M, et al. (2011) Nrf2 induces interleukin-6 (IL-6) expression via an antioxidant response element within the IL-6 promoter. J Biol Chem 286: 4493–4499. doi: 10.1074/jbc.m110.162008
[49]  García-Bermudez M, López-Mejías R, González-Juanatey C, Corrales A, Robledo G, et al. (2012) Analysis of the Interferon gamma (rs2430561, +874T/A) functional gene variant in relation to the presence of cardiovascular events in rheumatoid arthritis. Plos One 7: e47166. doi: 10.1371/journal.pone.0047166
[50]  Bogdan C (2001) Nitric oxide and the immune response. Nature immunology 2: 907–916. doi: 10.1038/ni1001-907
[51]  T?temeyer S, Sheppard M, Lloyd A, Roper D, Dowson C, et al. (2006) IFN-γ enhances production of nitric oxide from macrophages via a mechanism that depends on nucleotide oligomerization domain-2. J Immunol 176: 4804–4810. doi: 10.4049/jimmunol.176.8.4804
[52]  Stone TW, Darlington LG (2002) Endogenous kynurenines as targets for drug discovery and development. Nat Rev Drug Discov 1: 609–620. doi: 10.1038/nrd870
[53]  Sasaki M, Ozawa Y, Kurihara T, Noda K, Imamura Y, et al. (2009) Neuroprotective effect of an antioxidant, lutein, during retinal inflammation. Invest Ophthalmol Vis Sci 50: 1433–1439. doi: 10.1167/iovs.08-2493
[54]  Cano L, Thimmalappula R, Fujihara M, Nagai N, Sporn M, et al. (2010) Cigarette smoking, oxidative stress, the anti-oxidant response through Nrf2 signaling, and Age-related Macular Degeneration. Vis Res 50: 652–664. doi: 10.1016/j.visres.2009.08.018
[55]  Field MG, Yang D, Bian Z, Petty HR, Elner VM (2011) Retinal Flavoprotein Fluorescence Correlates with Mitochondrial Stress, Apoptosis, and Chemokine Expression. Exp Eye Res 93: 548–555. doi: 10.1016/j.exer.2011.06.023
[56]  Arima Y, Harada M, Kamimura D, Park JH, Kawano F, et al. (2012) Regional neural activation defines a gateway for autoreactive T cells to cross the blood-brain barrier. Cell 148: 447–457. doi: 10.1016/j.cell.2012.01.022
[57]  Omari KM, Lutz SE, Santambrogio L, Lira SA, Raine CS (2009) Neuroprotection and remyelination after autoimmune demyelination in mice that inducibly overexpress CXCL1. Am J Clin Pathol 174: 164–176. doi: 10.2353/ajpath.2009.080350
[58]  Vignali DAA, Collinson LW, Workman CJ (2008) How regulatory T cells work. Nat Rev Immunol 8: 523–532. doi: 10.1038/nri2343
[59]  Pandiyan P, Zheng L, Ishihara S, Reed J, Lenardo MJ (2007) CD4+CD25+Foxp3+ regulatory T cells induce cytokine deprivation–mediated apoptosis of effector CD4+ T cells. Nature Immun 8: 1353–1362. doi: 10.1038/ni1536
[60]  Tiemessen MM, Jagger AL, Evans HG, van Herwijnen MJC, John S, et al. (2007) CD4+CD25+Foxp3+ regulatory T cells induce alternative activation of human monocytes/macrophages. PNAS 104: 19446–19451. doi: 10.1073/pnas.0706832104
[61]  Kraaija MD, Savageb NDL, van der Kooija SW, Koekkoeka K, Wangc J, et al. (2010) Induction of regulatory T cells by macrophages is dependent on production of reactive oxygen species. PNAS 107: 17686–17691.
[62]  Kimura A, Kishimoto T (2010) IL-6: Regulator of Treg/Th17 balance. Eur J Immunol 40: 1830–1835. doi: 10.1002/eji.201040391

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