{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T17:28:47Z","timestamp":1777829327619,"version":"3.51.4"},"reference-count":38,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T00:00:00Z","timestamp":1425340800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013704","name":"CONACyT","doi-asserted-by":"publisher","award":["71291"],"award-info":[{"award-number":["71291"]}],"id":[{"id":"10.13039\/501100013704","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Corneal infections are frequent and potentially vision-threatening diseases, and despite the significance of the immunological response in animal models of microbial keratitis (MK), it remains unclear in humans. The aim of this study was to describe the cytokine profile of tears in patients with MK. Characteristics of ocular lesions such as size of the epithelial defect, stromal infiltration, and hypopyon were analyzed. Immunological evaluation included determination of interleukine (IL)-1\u03b2, IL-6, IL-8, IL-10, IL-12 and tumor necrosis factor (TNF)-\u03b1 in tear samples obtained from infected eyes of 28 patients with MK and compared with their contralateral non-infected eyes. Additionally, frequency of CD4+, CD8+, CD19+ and CD3\u2212CD56+ cells was also determined in peripheral blood mononuclear cells in patients with MK, and compared with 48 healthy controls. Non-significant differences were observed in the size of the epithelial defect, stromal infiltration, and hypopyon. Nevertheless, we found an immunological profile apparently related to MK etiology. IL-8 &gt; IL-6 in patients with bacterial keratitis; IL-8 &gt; IL-6 &gt; IL-1\u03b2 and increased frequency of circulating CD3\u2212CD56+ NK cells in patients with gram-negative keratitis; and IL-8 = IL-6 &gt; IL-1\u03b2 in patients with fungal keratitis. Characterization of tear cytokines from patients with MK could aid our understanding of the immune pathophysiological mechanisms underlying corneal damage in humans.<\/jats:p>","DOI":"10.3390\/ijms16034850","type":"journal-article","created":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T10:10:05Z","timestamp":1425377405000},"page":"4850-4864","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Expression of IL-8, IL-6 and IL-1\u03b2 in Tears as a Main Characteristic of the Immune Response in Human  Microbial Keratitis"],"prefix":"10.3390","volume":"16","author":[{"given":"Concepcion","family":"Santacruz","sequence":"first","affiliation":[{"name":"Cornea and Refractive Surgery Department, and Research Unit,  Institute of Ophthalmology \"Conde de Valenciana Foundation\", Mexico 06800, DF, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marisela","family":"Linares","sequence":"additional","affiliation":[{"name":"Cornea and Refractive Surgery Department, and Research Unit,  Institute of Ophthalmology \"Conde de Valenciana Foundation\", Mexico 06800, DF, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yonathan","family":"Garfias","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, National Autonomous University of Mexico, P.O. Box 70159, Mexico 04510, DF, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa","family":"Loustaunau","sequence":"additional","affiliation":[{"name":"Cornea and Refractive Surgery Department, and Research Unit,  Institute of Ophthalmology \"Conde de Valenciana Foundation\", Mexico 06800, DF, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6067-6868","authenticated-orcid":false,"given":"Lenin","family":"Pavon","sequence":"additional","affiliation":[{"name":"Department of Psychoimmunology, National Institute of Psychiatry \"Ram\u00f3n de la Fuente\",  Calzada M\u00e9xico-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, Mexico City 14370, DF,  Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia","family":"Perez-Tapia","sequence":"additional","affiliation":[{"name":"Unit of R&D in Bioprocesses (UDIBI), Department of Immunology,  National School of Biological Sciences, National Polytechnic Institute, Mexico 11340, DF, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3982-9097","authenticated-orcid":false,"given":"Maria","family":"Jimenez-Martinez","sequence":"additional","affiliation":[{"name":"Cornea and Refractive Surgery Department, and Research Unit,  Institute of Ophthalmology \"Conde de Valenciana Foundation\", Mexico 06800, DF, Mexico"},{"name":"Department of Biochemistry, Faculty of Medicine, National Autonomous University of Mexico, P.O. Box 70159, Mexico 04510, DF, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2015,3,3]]},"reference":[{"key":"ref_1","first-page":"214","article-title":"Corneal blindness. A global perspective","volume":"79","author":"Whitcher","year":"2001","journal-title":"Bull. World Health Organ."},{"key":"ref_2","unstructured":"World Health Organization Global Initiative for the Elimination of Avoidable Blindness: Action plan 2006\u20132011, Vision 2020. Available online: http:\/\/apps.who.int\/iris\/bitstream\/10665\/43754\/1\/9789241595889_eng.pdf?ua=1."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"114","DOI":"10.4103\/0974-620X.57310","article-title":"Epidemiological profile of fungal keratitis in urban population of West Bengal, India","volume":"2","author":"Saha","year":"2009","journal-title":"Oman J. Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1111\/j.1444-0938.2010.00511.x","article-title":"The patterns of in vitro antimicrobial susceptibility and resistance of bacterial keratitis isolates in Glasgow, United Kingdom","volume":"93","author":"Reeks","year":"2010","journal-title":"Clin. Exp. Optom."},{"key":"ref_5","first-page":"264","article-title":"Epidemiological features and laboratory results of bacterial and fungal keratitis: A five-year study at a rural tertiary-care hospital in western Maharashtra, India","volume":"53","author":"Deorukhkar","year":"2012","journal-title":"Singap. Med. J."},{"key":"ref_6","first-page":"273","article-title":"Review of epidemiological features, microbiological diagnosis and treatment outcome of microbial keratitis: Experience of over a decade Indian","volume":"57","author":"Gopinathan","year":"2009","journal-title":"J. Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1136\/bjo.87.7.834","article-title":"Bacterial keratitis: Predisposing factors, clinical and microbiological review of 300 cases","volume":"87","author":"Bourcier","year":"2003","journal-title":"Br. J. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1136\/bjo.81.8.622","article-title":"Corneal ulceration in developing world: A silent epidemic","volume":"81","author":"Whitcher","year":"1997","journal-title":"Br. J. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"159","DOI":"10.3109\/09286589609080122","article-title":"Incidence of corneal ulceration in Madurai District, South India","volume":"3","author":"Gonzales","year":"1996","journal-title":"Ophthalmic Epidemiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1097\/ICO.0b013e31825694d3","article-title":"Seasonal trends of microbial keratitis in South India","volume":"31","author":"Lin","year":"2012","journal-title":"Cornea"},{"key":"ref_11","first-page":"213","article-title":"Infectious keratitis: microbiological and antibiotic sensitivity trends. First annual report of the Ocular Microbiology Study Group from the Instituto de Oftalmolog\u00eda \u201cConde de Valenciana\u201d","volume":"86","author":"Navas","year":"2012","journal-title":"Rev. Mex. Oftalmol."},{"key":"ref_12","first-page":"100","article-title":"Infectious keratitis: Microbiological and antibiotic sensitivity trends. Second Annual Report of the Ocular Microbiology Study Group from the Instituto de Oftalmologia \u201cConde de Valenciana\u201d","volume":"87","author":"Navas","year":"2013","journal-title":"Rev. Mex. Oftalmol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4272","DOI":"10.4049\/jimmunol.1000874","article-title":"TLR4 and TLR5 on corneal macrophages regulate Pseudomonas aeruginosa keratitis by signaling through MyD88-dependent and -independent pathways","volume":"185","author":"Sun","year":"2010","journal-title":"J. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1167\/iovs.09-4237","article-title":"A murine model of contact lens-associated fusarium keratitis","volume":"51","author":"Sun","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_15","first-page":"38","article-title":"Activation of the lectin pathway of complement in experimental human keratitis with Pseudomonas aeruginosa","volume":"20","author":"Osthoff","year":"2014","journal-title":"Mol. Vis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4103\/0301-4738.29491","article-title":"A pilot study on the infiltrating cells and cytokine levels in the tear of fungal keratitis patients","volume":"55","author":"Vasanthi","year":"2007","journal-title":"Indian J. Ophthalmol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7457","DOI":"10.1167\/iovs.14-15411","article-title":"Correlation between human tear cytokine levels and cellular corneal changes in patients with bacterial keratitis by in vivo confocal microscopy","volume":"55","author":"Yamaguchi","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1167\/iovs.11-8478","article-title":"The clinical differentiation of bacterial and fungal keratitis: A photographic survey","volume":"53","author":"Dalmon","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1016\/j.ajo.2007.02.030","article-title":"The clinical diagnosis of microbial keratitis","volume":"143","author":"Matthew","year":"2007","journal-title":"Am. J. Ophthalmol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1097\/ICO.0b013e3181f23704","article-title":"Clinical aspects and prognosis of mixed microbial (bacterial and fungal) keratitis","volume":"30","author":"Ahn","year":"2011","journal-title":"Cornea"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1097\/00055735-199808000-00008","article-title":"Current diagnosis and treatment of corneal ulcers","volume":"9","author":"Benson","year":"1998","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1097\/ICO.0b013e318156caf2","article-title":"Risk factors and causative organisms in microbial keratitis","volume":"27","author":"Green","year":"2008","journal-title":"Cornea"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.ophtha.2005.08.013","article-title":"Microbial keratitis predisposing factors and morbidity","volume":"113","author":"Keay","year":"2006","journal-title":"Ophthalmology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1590\/S0004-27492010000400002","article-title":"Microbial keratitis in the elderly: A 32-year review","volume":"73","author":"Passos","year":"2010","journal-title":"Arq. Bras. Oftalmol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1365-2567.2005.02256.x","article-title":"Putting the natural killer cell in its place","volume":"117","author":"Hart","year":"2006","journal-title":"Immunology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"473097","DOI":"10.1155\/2011\/473097","article-title":"Role of natural killer and dendritic cell crosstalk in immunomodulation by commensal bacteria probiotics","volume":"2011","author":"Rizzello","year":"2011","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1002\/eji.200425902","article-title":"Substance p regulates natural killer cell interferon-\u03b3 production and resistance to pseudomonas aeruginosa infection","volume":"35","author":"Lighvani","year":"2005","journal-title":"Eur. J. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.4049\/jimmunol.179.2.1138","article-title":"NKT cells are critical to initiate an inflammatory response after Pseudomonas aeruginosa ocular infection in susceptible mice","volume":"179","author":"Hazlett","year":"2007","journal-title":"J. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.preteyeres.2003.10.002","article-title":"Corneal response to Pseudomonas aeruginosa infection","volume":"23","author":"Hazlett","year":"2004","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1073\/pnas.1012356108","article-title":"Revisiting human natural killer cell subset function revealed cytolytic CD56(dim)CD16+ NK cells as rapid producers of abundant IFN-\u03b3 on activation","volume":"108","author":"Bozzano","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2594","DOI":"10.1001\/jama.2011.1829","article-title":"Immunosuppression in patients who die of sepsis and multiple organ failure","volume":"306","author":"Boomer","year":"2011","journal-title":"JAMA"},{"key":"ref_32","first-page":"83","article-title":"Phagocytosis of particulate antigens by corneal epithelial cells stimulates interleukin-1 secretion and migration of Langerhans cells into the central cornea","volume":"2","author":"Niederkorn","year":"1989","journal-title":"Reg. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1189\/jlb.0911458","article-title":"Tissue stroma as a regulator of leukocyte recruitment in inflammation","volume":"91","author":"McGettrick","year":"2012","journal-title":"J. Leukoc. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"401","DOI":"10.3109\/09273948.2011.618902","article-title":"Roles of IL-8 in ocular inflammations: A review","volume":"19","author":"Ghasemi","year":"2011","journal-title":"Ocul. Immunol. Inflamm."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1093\/infdis\/jir426","article-title":"Expression of innate and adaptive immune mediators in human corneal tissue infected with Aspergillus or Fusarium","volume":"204","author":"Karthikeyan","year":"2011","journal-title":"J. Infect Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1111\/cei.12295","article-title":"Interleukin-6 blockade in ocular inflammatory diseases","volume":"176","author":"Mesquida","year":"2014","journal-title":"Clin. Exp. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1093\/rheumatology\/ken489","article-title":"Involvement of Th17 cells and the effect of anti-IL-6 therapy in autoimmune uveitis","volume":"48","author":"Yoshimura","year":"2009","journal-title":"Rheumatology (Oxford)"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.exer.2012.02.015","article-title":"Anti-inflammatory effect of IL-6 receptor blockade in corneal alkali burn","volume":"97","author":"Sakimoto","year":"2012","journal-title":"Exp. Eye Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/16\/3\/4850\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:43:04Z","timestamp":1760215384000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/16\/3\/4850"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3,3]]},"references-count":38,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2015,3]]}},"alternative-id":["ijms16034850"],"URL":"https:\/\/doi.org\/10.3390\/ijms16034850","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3,3]]}}}