Expression of cytokines in aqueous humor from fungal keratitis patients

Yingnan Zhang, Qingfeng Liang, Yang Liu, Zhiqiang Pan, Christophe Baudouin, Antoine Labbé, Qingxian Lu, Yingnan Zhang, Qingfeng Liang, Yang Liu, Zhiqiang Pan, Christophe Baudouin, Antoine Labbé, Qingxian Lu

Abstract

Background: Although a series of reports on corneal fungal infection have been published, studies on pathogenic mechanisms and inflammation-associated cytokines remain limited. In this study, aqueous humor samples from fungal keratitis patients were collected to examine cytokine patterns and cellular profile for the pathogenesis of fungal keratitis.

Methods: The aqueous humor samples were collected from ten patients with advanced stage fungal keratitis. Eight aqueous humor samples from patients with keratoconus or corneal dystrophy were taken as control. Approximately 100 μl to 300 μl of aqueous humor in each case were obtained for examination. The aqueous humor samples were centrifuged and the cells were stained and examined under optical microscope. Bacterial and fungal cultures were performed on the aqueous humor and corneal buttons of all patients. Cytokines related to inflammation including IL-1β, IL-6, IL-8, IL-10, TNF-α, and IFN-γ were examined using multiplex bead-based Luminex liquid protein array systems.

Results: Fungus infection was confirmed in these ten patients by smear stains and/or fungal cultures. Bacterial and fungal cultures revealed negative results in all aqueous humor specimens. Polymorphonuclear leukocytes were the predominant infiltrating cells in the aqueous humor of fungal keratitis. At the advanced stages of fungal keratitis, the levels of IL-1β, IL-6, IL-8, and IFN-γ in the aqueous humor were significantly increased when compared with control (p<0.01). The levels of IL-10 and TNF-α also showed an ascending trend but with no statistical significance.

Conclusions: High concentration of IL-1β, IL-6, IL-8, and IFN-γ in the aqueous humor was associated with fungal keratitis.

Keywords: aqueous humor; cytokines; fungal keratitis; inflammation.

Conflict of interest statement

Ethics approval and consent to participate

The study was approved by the Institutional Review Board and Ethics Committee of Beijing Tongren Hospital. Informed consent was obtained from all individual participants and parents/legal guardians in the study.

Consent for publication

Not Applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

    1. Whitcher JP, Srinivasan M, Upadhyay MP. Corneal blindness: a global perspective. Bull World Health Organ. 2001;79(3):214–221.
    1. Whitcher JP, Srinivasan M. Corneal ulceration in the developing world--a silent epidemic. Br J Ophthalmol. 1997;81(8):622–623. doi: 10.1136/bjo.81.8.622.
    1. Dong X, Xie L, Shi W. Penetrating keratoplasty in management of fungal keratitis. Chin J Ophthalmol. 1994;35:386–387.
    1. Xie L, Zhong W, Shi W. Spectrum of fungal keratitis in north China. Ophthalmol. 2006;113:1943–1948. doi: 10.1016/j.ophtha.2006.05.035.
    1. Prajna NV, John RK, Nirmalan PK, Lalitha P, Srinivasan M. A randomised clinical trial comparing 2% econazole and 5% natamycin for the treatment of fungal keratitis. Br J Ophthalmol. 2003;87(10):1235–1237. doi: 10.1136/bjo.87.10.1235.
    1. Thomas PA. Current perspectives on ophthalmic mycoses. Clin Microbiol Rev. 2003;16(4):730–797. doi: 10.1128/CMR.16.4.730-797.2003.
    1. Wu TG, Wilhelmus KR, Mitchell BM. Experimental keratomycosis in a mouse model. Invest Ophthalmol Vis Sci. 2003;44(1):210–216. doi: 10.1167/iovs.02-0446.
    1. Wu TG, Keasler VV, Mitchell BM, Wilhelmus KR. Immunosuppression affects the severity of experimental Fusarium solani keratitis. J Infect Dis. 2004;190(1):192–198. doi: 10.1086/421300.
    1. Vasanthi M, Prajna NV, Lalitha P, Mahadevan K, Muthukkaruppan V. A pilot study on the infiltrating cells and cytokine levels in the tear of fungal keratitis patients. Indian J Ophthalmol. 2007;55(1):27–31. doi: 10.4103/0301-4738.29491.
    1. Vemuganti GK, Garg P, Gopinathan U, Naduvilath TJ, John RK, Buddi R, Rao GN. Evaluation of agent and host factors in progression of mycotic keratitis: A histologic and microbiologic study of 167 corneal buttons. Ophthalmology. 2002;109(8):1538–1546. doi: 10.1016/S0161-6420(02)01088-6.
    1. Thomas J, Gangappa S, Kanangat S, Rouse BT. On the essential involvement of neutrophils in the immunopathologic disease: herpetic stromal keratitis. Journal of immunology (Baltimore, Md : 1950) 1997;158(3):1383–1391.
    1. Becker J, Salla S, Dohmen U, Redbrake C, Reim M. Explorative study of interleukin levels in the human cornea. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 1995;233(12):766–771. doi: 10.1007/BF00184087.
    1. Yamaguchi T, Calvacanti BM, Cruzat A, Qazi Y, Ishikawa S, Osuka A, Lederer J, Hamrah P. Correlation between human tear cytokine levels and cellular corneal changes in patients with bacterial keratitis by in vivo confocal microscopy. Invest Ophthalmol Vis Sci. 2014;55(11):7457–7466. doi: 10.1167/iovs.14-15411.
    1. Imanishi J. Expression of cytokines in bacterial and viral infections and their biochemical aspects. J Biochem. 2000;127(4):525–530. doi: 10.1093/oxfordjournals.jbchem.a022636.
    1. Stumpf TH, Shimeld C, Easty DL, Hill TJ. Cytokine production in a murine model of recurrent herpetic stromal keratitis. Invest Ophthalmol Vis Sci. 2001;42(2):372–378.
    1. Xue ML, Willcox MD, Lloyd A, Wakefield D, Thakur A. Regulatory role of IL-1beta in the expression of IL-6 and IL-8 in human corneal epithelial cells during Pseudomonas aeruginosa colonization. Clin Exp Ophthalmol. 2001;29(3):171–174. doi: 10.1046/j.1442-9071.2001.00410.x.
    1. van Kooij B, Rothova A, Rijkers GT, de Groot-Mijnes JD. Distinct cytokine and chemokine profiles in the aqueous of patients with uveitis and cystoid macular edema. Am J Ophthalmol. 2006;142(1):192–194. doi: 10.1016/j.ajo.2006.02.052.
    1. Hamzaoui K, Hamzaoui A, Guemira F, Bessioud M, Hamza M, Ayed K. Cytokine profile in Behcet's disease patients. Relationship with disease activity. Scand J Rheumatol. 2002;31(4):205–210. doi: 10.1080/030097402320318387.
    1. Ahn JK, Yu HG, Chung H, Park YG. Intraocular cytokine environment in active Behcet uveitis. Am J Ophthalmol. 2006;142(3):429–434. doi: 10.1016/j.ajo.2006.04.016.
    1. van Gelderen BE, Van Der Lelij A, Peek R, Broersma L, Treffers WF, Ruijter JM, van Der Gaag R. Cytokines in aqueous humour and serum before and after corneal transplantation and during rejection. Ophthalmic Res. 2000;32(4):157–164. doi: 10.1159/000055607.
    1. Dinarello CA. Biologic basis for interleukin-1 in disease. Blood. 1996;87(6):2095–2147.
    1. Rudner XL, Kernacki KA, Barrett RP, Hazlett LD. Prolonged elevation of IL-1 in Pseudomonas aeruginosa ocular infection regulates macrophage-inflammatory protein-2 production, polymorphonuclear neutrophil persistence, and corneal perforation. Journal of immunology (Baltimore, Md : 1950) 2000;164(12):6576–6582. doi: 10.4049/jimmunol.164.12.6576.
    1. Fenton RR, Molesworth-Kenyon S, Oakes JE, Lausch RN. Linkage of IL-6 with neutrophil chemoattractant expression in virus-induced ocular inflammation. Invest Ophthalmol Vis Sci. 2002;43(3):737–743.
    1. Maruo N, Morita I, Shirao M, Murota S. IL-6 increases endothelial permeability in vitro. Endocrinology. 1992;131(2):710–714.
    1. Noma H, Funatsu H, Yamasaki M, Tsukamoto H, Mimura T, Sone T, Jian K, Sakamoto I, Nakano K, Yamashita H, et al. Pathogenesis of macular edema with branch retinal vein occlusion and intraocular levels of vascular endothelial growth factor and interleukin-6. Am J Ophthalmol. 2005;140(2):256–261. doi: 10.1016/j.ajo.2005.03.003.
    1. Chodosh J, Astley RA, Butler MG, Kennedy RC. Adenovirus keratitis: a role for interleukin-8. Invest Ophthalmol Vis Sci. 2000;41(3):783–789.
    1. Oakes JE, Monteiro CA, Cubitt CL, Lausch RN. Induction of interleukin-8 gene expression is associated with herpes simplex virus infection of human corneal keratocytes but not human corneal epithelial cells. J Virol. 1993;67(8):4777–4784.
    1. Macatonia SE, Doherty TM, Knight SC, O'Garra A. Differential effect of IL-10 on dendritic cell-induced T cell proliferation and IFN-gamma production. Journal of immunology (Baltimore, Md : 1950) 1993;150(9):3755–3765.
    1. Boorstein SM, Elner SG, Meyer RF, Sugar A, Strieter RM, Kunkel SL, Elner VM. Interleukin-10 inhibition of HLA-DR expression in human herpes stromal keratitis. Ophthalmology. 1994;101(9):1529–1535. doi: 10.1016/S0161-6420(94)31149-3.
    1. 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(5):251–255. doi: 10.1159/000055677.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel