Contents lists available at ScienceDirect International Immunopharmacology journal homepage: www.elsevier.com/locate/intimp TearandserumMMP-9andserumTIMPslevelsintheseveresulfurmustard eye injured exposed patients Hassan Ghasemi a , Roya Yaraee b,c , Soghrat Faghihzadeh d , Mohammad Ghassemi-Broumand e , Mahmoud Mahmoudi f , Mahmoud Babaei g,h , Mostafa Naderi h,i , Maliheh Safavi j , Zeinab Ghazanfari k , Maryam Rastin f , Shahrzad Zamani l , Nafseh Tabasi m , Elham Faghihzadeh c , Reza Gharebaghi n , Zuhair Mohammad Hassan o , Ensie sadat Mirsharif c , Tooba Ghazanfari b,c, ⁎ a Department of Ophthalmology, Shahed University, Tehran, Iran b Department of Immunology, Shahed University, Tehran, Iran c Immunoregulation Research Center, Shahed University, Tehran, Iran d Department of Biostatistics and Social Medicine, Zanjan University of Medical Sciences, Zanjan, Iran e Department of Optometry, Faculty of Rehabilitation, Shahid Beheshti University (M.C), Tehran, Iran f Immunology Research Center, Department of Immunology and Allergy, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran g Department of Ophthalmology, Baqiyatallah University of Medical Sciences, Tehran, Iran h Trauma Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran i Department of Epidemiology, Baqiyatallah University of Medical Science, Tehran, Iran j Department of Biotechnology, Iranian Research Organization for Science and Technology, Tehran, Iran k Department of Health Education and Promotion, Faculty of Health, Ilam University of Medical Sciences l School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC, 3168, Australia m Immunology Research Center, BuALi Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran n International Virtual Ophthalmic Research Center, Tehran, Iran o Department of Immunology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran ARTICLEINFO Keywords: Sulfur mustard Ocular injury Matrix metalloproteinase-9 (MMP-9) Tissueinhibitorsofmetalloproteinase-1(TIMP-1) Tissueinhibitorsofmetalloproteinase-4(TIMP-4) ABSTRACT Introduction: Sulfur mustard (SM) intoxication produces local and systemic changes in the human body. In this study,therelationshipbetweentearandserummatrixmetalloproteinase(MMP)-9andserumtissueinhibitorsof metalloproteinases (TIMPs) are assessed in serious eye-injured SM-exposed casualties. Methods: A group of 128 SM-exposed patients with serious ocular injuries in three subgroups (19 mild, 31 moderate, and 78 severe cases) is compared with 31 healthy controls. Tear and ocular status and serum MMPs and MMP-9/TIMPs complex levels were evaluated using enzyme-linked immunosorbent assay (ELISA). Results: SerumlevelofMMP-9wassignifcantly higher in the SM-exposed group compared to the control group (P=0.009). Mean serum MMP-9 level in the SM-exposed group with ocular abnormalities was signifcantly higher than that in the SM-exposed group without ocular abnormalities. SM-exposed people with corneal cal- cifcation had signifcantly higher serum MMP-9/TIMP-1 level compared to the SM-exposed ones without this problem(P=0.045).TheSM-exposedgroupwithsevereocularinjurieshadsignifcantlyhigherMMP-9/TIMP-1 thanthecontrols(P=0.046).TheSM-exposedgrouphadsignifcantlylowerlevelsof MMP-9/TIMP-4 complex than the controls (P < 0.001). The SM-exposed group with tear meniscus and fundus abnormality had sig- nifcantly higher MMP-9/TIMP-4 levels than the SM-exposed group without these problems (P=0.009 and P=0.020). Conclusion: Serum MMP-9 level had increased in SM-exposed groups with ocular problems, while TIMP-1 and TIMP-2 levels had remained unchanged. Serum TIMP-4 drastically decreased in SM-exposed group, which clearly explains the severity of the systemic and ocular damages. https://doi.org/10.1016/j.intimp.2019.105812 Received 2 June 2019; Received in revised form 5 August 2019; Accepted 5 August 2019 ⁎ Corresponding author: Tooba Ghazanfari, Immunoregulation Research Center and Dep of Immunology, Shahed University, Tehran, Iran. E-mail addresses: mahmoudi@mums.ac.ir (M. Mahmoudi), irrc@shahed.ac.ir (M. Babaei), Ghazanfari-z@meilam.ac.ir (Z. Ghazanfari), Rastinm@mums.ac.ir (M. Rastin), Shahrzad.zamanitaghizadehrabe@monash.edu (S. Zamani), Tabasin1@mums.ac.ir (N. Tabasi), hasan_zm@modares.ac.ir (Z.M. Hassan), ghazanfari@shahed.ac.ir (T. Ghazanfari). International Immunopharmacology 77 (2019) 105812 1567-5769/ © 2019 Elsevier B.V. All rights reserved. T