Changes in matrix metalloproteinases and their inhibitors in the tears and blood serum of patients with herpetic keratoconjunctivitis under the influence of antiherpetic antibodies and nimesulide

Authors

DOI:

https://doi.org/10.14739/2310-1237.2021.1.220205

Keywords:

infectious keratoconjunctivitis, matrix metalloproteinases, matrix metalloproteinases inhibitors, immunoglobulin, nimesulide, herpetic keratitis

Abstract

Aim. The aim of the study was to study changes in matrix metalloproteinases and their tissue inhibitors in the tears and blood serum of patients with herpetic keratoconjunctivitis under the influence of antiherpetic antibodies and nimesulide.

Materials and methods.65 adult patients with herpetic keratoconjunctivitis (HKC) caused by the herpes simplex virus type 1 (HSV-1) were examined. The etiological diagnosis of HKC was confirmed by polymerase chain reaction.

The control group consisted of 32 patients who received basic treatment with acyclovir and interferon in the affected eye. The main group consisted of 33 patients who received antiherpetic immunoglobulin and nimesulide in addition to basic therapy. Immunoglobulin was administered intramuscularly and instilled into the affected eye, and nimesulide was administered orally. The control group consisted of 38 practically healthy adults.

Matrix metalloproteinases MMP-1, MMP-8, and MMP-9 and their tissue inhibitors TIMP-1 and TIMP-2 were determined by solid-phase enzyme immunoassay in the tear fluid and blood serum of patients. The results of the study were processed according to the Student's criterion.

Results. With HKC in the affected eye, in the acute phase of the disease, there are: an increase in the concentrations of MMP-1, MMP-8, MMP-9, both in the tear fluid and in the blood serum of patients; a decrease in the concentrations of TIMP-1 and TIMP-2 in the tear fluid, with unchanged levels of these compounds in the blood serum; violation of the balance in the corresponding MMP/TIMP systems to the advantage of MMP. In the convalescence phase, these shifts in the concentrations of MMPs, TIMPs and the balance between them significantly decrease, but their complete normalization does not occur, which is most significant for tear fluid than for the blood serum of convalescents.

The combination of antiherpetic immunoglobulin and nimesulide helps to inhibit the exces production of MMP-1, MMP-8, MMP-9 in the lacrimal fluid of the causal eye and in the blood serum of patients, optimizes the level of TIMP-1, TIMP-2 and balance in the corresponding MMPs/TIMPs systems.

Conclusion. In the acute phase of SCC, MMPs activity prevails, in the convalescence phase, TIMPs activity prevails. The combination of antiherpetic immunoglobulin and nimesulide has a positive effect on the state of MMPs and TIMPs in the lacrimal fluid of the causal eye and in the blood serum of patients.

Author Biographies

P. H. Pantielieiev, SI “Luhansk State Medical University”, Rubizhne, Ukraine

Postgraduate Student of the Department of Normal Physiology and Pathophysiology

I. S. Haidash, State Institution “Lugansk State Medical University”, Rubizhne, Ukraine

MD, PhD, DSc, Professor, Honored Worker of Science and Technology of Ukraine, Head of the Department of Microbiology, Virology and Immunology

References

Pflipsen, M., Massaquoi, M., & Wolf, S. (2016). Evaluation of the Painful Eye. American family physician, 93(12), 991-998.

Sakovich, V. N., Nikitchina, T. S., & Shcherbakov, B. D. (2014). Gerpeticheskii keratit: etiologiya, patogenez, diagnostika, lechenie [Herpetic keratitis: etiology, pathogenesis, diagnosis, treatment]. Oftal'mologicheskii zhurnal, (5), 70-80. [in Russian].

Rabenau, H. F., Buxbaum, S., Preiser, W., Weber, B., & Doerr, H. W. (2002). Seroprevalence of herpes simplex virus types 1 and type 2 in the Frankfurt am Main area, Germany. Medical microbiology and immunology, 190(4), 153-160. https://doi.org/10.1007/s00430-001-0102-1

Xu, F., Sternberg, M. R., Kottiri, B. J., McQuillan, G. M., Lee, F. K., Nahmias, A. J., Berman, S. M., & Markowitz, L. E. (2006). Trends in herpes simplex virus type 1 and type 2 seroprevalence in the United States. JAMA, 296(8), 964-973. https://doi.org/10.1001/jama.296.8.964

Kong, C. L., Thompson, R. R., Porco, T. C., Kim, E., & Acharya, N. R. (2020). Incidence Rate of Herpes Zoster Ophthalmicus: A Retrospective Cohort Study from 1994 through 2018. Ophthalmology, 127(3), 324-330. https://doi.org/10.1016/j.ophtha.2019.10.001

Davies, E. C., Pavan-Langston, D., & Chodosh, J. (2016). Herpes zoster ophthalmicus: declining age at presentation. The British journal of ophthalmology, 100(3), 312-314. https://doi.org/10.1136/bjophthalmol-2015-307157

Drozhzhina G. I., Gaidamaka T. B. (2012). Osobennosti klinicheskogo techeniya i lecheniya keratita, vyzvannogo virusom Varicellazoster [The peculiarities of the clinical course and treatment of herpes zoster keratitis]. Oftal'mologicheskii zhurnal, (1), 9-13. [in Russian].

Drozhzhina, G. I., Gaidamaka, T. B., & Velichko, L. N. (2013). Soderzhanie interferonov v sleznoi zhidkosti pod vliyaniem induktora interferona u bol'nykh adenovirunym keratokon"yunktivitom [A content of interferons in the tear fluid under the influence of the interferon inductor in patients with adenoviral keratoconjunctivitis]. Oftal'mologicheskii zhurnal, (5), 5-8. [in Russian].

Khramenko, N. I., Ponomarchuk, V. S., Gajdamaka, T. B., & Drozhzhina, G. I. (2013). Osobennosti sostoyaniya vegetativnoi nervnoi sistemy i ee vliyanie na regionarnuyu gemodinamiku glaza u bol'nykh s razlichnym kharakterom techeniya retsidiviruyushchego gerpeticheskogo keratita [Peculiarities of the condition of the vegetative nervous system and its influence on the eye regional hemodynamics in patients with various character of recurrent herpetic keratitis course]. Oftal'mologicheskii zhurnal, (6), 5-12. [in Russian].

Gaydash, I. S., & Panteleev. P. G. (2016). Aktivnost' perekisnogo okislenija lipidov i antioksidantnoj sistemy v sljoznoj zhidkosti i syvorotke krovi bol'nyh oftal'mogerpesom [Activity of lipid peroxidation and antioxidant system in the tear fluid and serum of patients with ophthalmic herpes]. Medytsyna sohodni i zavtra, (2-3), 68-70. [in Russian].

Gaidamaka, T. B., Drozhzhina, G. I., Khramenko, N. I., & Dumbrova, N. E. (2010). Vzaimosvjaz' kliniko-funkcional'nyh projavlenij i patomorfologicheskih izmenenij rogovicy u bol'nyh gerpeticheskim keratitom [Interrelation of clinical and functional manifestations and pathomorphological changes of the cornea in patients with herpetic keratitis]. Oftal'mologicheskii zhurnal, (5), 12-16. [in Russian].

Van Doren S. R. (2015). Matrix metalloproteinase interactions with collagen and elastin. Matrix biology, 44-46, 224-231. https://doi.org/10.1016/j.matbio.2015.01.005

Kapoor, C., Vaidya, S., Wadhwan, V., Hitesh, Kaur, G., & Pathak, A. (2016). Seesaw of matrix metalloproteinases (MMPs). Journal of cancer research and therapeutics, 12(1), 28-35. https://doi.org/10.4103/0973-1482.157337

Cui, N., Hu, M., & Khalil, R. A. (2017). Biochemical and Biological Attributes of Matrix Metalloproteinases. Progress in molecular biology and translational science, 147, 1-73. https://doi.org/10.1016/bs.pmbts.2017.02.005

Nissinen, L., & Kähäri, V. M. (2014). Matrix metalloproteinases in inflammation. Biochimica et biophysica acta, 1840(8), 2571-2580. https://doi.org/10.1016/j.bbagen.2014.03.007

Tardáguila-García, A., García-Morales, E., García-Alamino, J. M., Álvaro-Afonso, F. J., Molines-Barroso, R. J., & Lázaro-Martínez, J. L. (2019). Metalloproteinases in chronic and acute wounds: A systematic review and meta-analysis. Wound repair and regeneration, 27(4), 415-420. https://doi.org/10.1111/wrr.12717

Fingleton B. (2017). Matrix metalloproteinases as regulators of inflammatory processes. Biochimica et biophysica acta. Molecular cell research, 1864(11 Pt A), 2036-2042. https://doi.org/10.1016/j.bbamcr.2017.05.010

Arpino, V., Brock, M., & Gill, S. E. (2015). The role of TIMPs in regulation of extracellular matrix proteolysis. Matrix biology, 44-46, 247-254. https://doi.org/10.1016/j.matbio.2015.03.005

Levin, M., Udi, Y., Solomonov, I., & Sagi, I. (2017). Next generation matrix metalloproteinase inhibitors - Novel strategies bring new prospects. Biochimica et biophysica acta. Molecular cell research, 1864(11 Pt A), 1927-1939. https://doi.org/10.1016/j.bbamcr.2017.06.009

Yan, C., Luo, Z., Li, W., Li, X., Dallmann, R., Kurihara, H., Li, Y. F., & He, R. R. (2020). Disturbed Yin-Yang balance: stress increases the susceptibility to primary and recurrent infections of herpes simplex virus type 1. Acta pharmaceutica Sinica. B, 10(3), 383-398. https://doi.org/10.1016/j.apsb.2019.06.005

Lobo, A. M., Agelidis, A. M., & Shukla, D. (2019). Pathogenesis of herpes simplex keratitis: The host cell response and ocular surface sequelae to infection and inflammation. The ocular surface, 17(1), 40-49. https://doi.org/10.1016/j.jtos.2018.10.002

Cabrera-Aguas, M., Robaei, D., McCluskey, P., & Watson, S. (2018). Clinical translation of recommendations from randomized trials for management of herpes simplex virus keratitis. Clinical & experimental ophthalmology, 46(9), 1008-1016. https://doi.org/10.1111/ceo.13319

Seitz, B., & Heiligenhaus, A. (2015). Das Chamäleon der Keratitis herpetischer Genese - Diagnose und Therapie [The Chameleon of Herpetic Keratitis - Diagnosis and Therapy]. Klinische Monatsblatter fur Augenheilkunde, 232(6), 745-753. [in German]. https://doi.org/10.1055/s-0035-1545975

Carter, S. B., & Cohen, E. J. (2016). Development of Herpes Simplex Virus Infectious Epithelial Keratitis During Oral Acyclovir Therapy and Response to Topical Antivirals. Cornea, 35(5), 692-695. https://doi.org/10.1097/ICO.0000000000000806

Pan, D., Kaye, S. B., Hopkins, M., Kirwan, R., Hart, I. J., & Coen, D. M. (2014). Common and new acyclovir resistant herpes simplex virus-1 mutants causing bilateral recurrent herpetic keratitis in an immunocompetent patient. The Journal of infectious diseases, 209(3), 345-349. https://doi.org/10.1093/infdis/jit437

Farooq A. V. (2017). Herpes Simplex Virus Keratitis and Resistance to Acyclovir. Cornea, 36(2), e4-e5. https://doi.org/10.1097/ICO.0000000000001100

Bhatt, U. K., Abdul Karim, M. N., Prydal, J. I., Maharajan, S. V., & Fares, U. (2016). Oral antivirals for preventing recurrent herpes simplex keratitis in people with corneal grafts. The Cochrane database of systematic reviews, 11(11), CD007824. https://doi.org/10.1002/14651858.CD007824.pub2

Roozbahani, M., & Hammersmith, K. M. (2018). Management of herpes simplex virus epithelial keratitis. Current opinion in ophthalmology, 29(4), 360-364. https://doi.org/10.1097/ICU.0000000000000483

Farooq, A. V., Paley, G. L., Lubniewski, A. J., Gonzales, J. A., & Margolis, T. P. (2018). Unilateral Posterior Interstitial Keratitis as a Clinical Presentation of Herpes Simplex Virus Disease. Cornea, 37(3), 375-378. https://doi.org/10.1097/ICO.0000000000001499

Gaidash, I. S., & Panteleev, P. G. (2017). Tsitokinovyi profil' syvorotki krovi i sleznoi zhidkosti u bol'nykh oftal'mogerpesom [Cytokine profile of blood serum and tear fluid in patients with ophthalmoherpes]. Medytsyna sohodni i zavtra, (3-4), 25-29. [in Russian].

Morion. (n.d.). Gammalin immunoglobulin cheloveka protiv virusa gerpesa prostogo I tipa [Gammalinum immunoglobulinum humanum contra herpes virus simplex typus 1]. Compendium. Medicines. https://compendium.com.ua/info/168223/gammalin-immunoglobulin-cheloveka-protiv-virusa-gerpesa-prostogo-i-tipa/

Likitoriya. (n.d.). Gammalin (Gamalin) Immunoglobulin protiv virusa gerpesa prostogo 1 tipa cheloveka [Gammalin human immunoglobulin against herpes simplex virus type 1]. https://likitoriya.com/goods/gammalin_immunoglobulin_protiv_virusa_gerpesa_prostogo.html

Directory Vidal "Medicines in Russia". (n.d.). Nimesil® (Nimesil) instruktsiya po primeneniyu [Nimesil® (Nimesil) instructions for use]. Vidal. Directory of medicines. [in Russian]. https://www.vidal.ru/drugs/nimesil__2208

Yang, Y. N., Bauer, D., Wasmuth, S., Steuhl, K. P., & Heiligenhaus, A. (2003). Matrix metalloproteinases (MMP-2 and 9) and tissue inhibitors of matrix metalloproteinases (TIMP-1 and 2) during the course of experimental necrotizing herpetic keratitis. Experimental Eye Research, 77(2), 227-237. https://doi.org/10.1016/S0014-4835(03)00112-X

Ke, L., Yang, Y., Li, J. W., Wang, B., Wang, Y., Yang, W., & Yan, J. (2019). Modulation of Corneal FAK/PI3K/Akt Signaling Expression and of Metalloproteinase-2 and Metalloproteinase-9 during the Development of Herpes Simplex Keratitis. BioMed research international, 2019, 4143981. https://doi.org/10.1155/2019/4143981

Yang, Y. N., Wang, F., Zhou, W., Wu, Z. Q., & Xing, Y. Q. (2012). TNF-α stimulates MMP-2 and MMP-9 activities in human corneal epithelial cells via the activation of FAK/ERK signaling. Ophthalmic research, 48(4), 165-170. https://doi.org/10.1159/000338819

Raeeszadeh-Sarmazdeh, M., Do, L. D., & Hritz, B. G. (2020). Metalloproteinases and Their Inhibitors: Potential for the Development of New Therapeutics. Cells, 9(5), 1313. https://doi.org/10.3390/cells9051313

Galvis, V., Sherwin, T., Tello, A., Merayo, J., Barrera, R., & Acera, A. (2015). Keratoconus: an inflammatory disorder?. Eye (London, England), 29(7), 843-859. https://doi.org/10.1038/eye.2015.63

Horwitz, V., Dachir, S., Cohen, M., Gutman, H., Cohen, L., Fishbine, E., Brandeis, R., Turetz, J., Amir, A., Gore, A., & Kadar, T. (2014). The beneficial effects of doxycycline, an inhibitor of matrix metalloproteinases, on sulfur mustard-induced ocular pathologies depend on the injury stage. Current eye research, 39(8), 803-812. https://doi.org/10.3109/02713683.2013.874443

Sakimoto, T., & Sawa, M. (2012). Metalloproteinases in corneal diseases: degradation and processing. Cornea, 31 Suppl 1, S50-S56. https://doi.org/10.1097/ICO.0b013e318269ccd0

Published

2021-05-18

How to Cite

1.
Pantielieiev PH, Haidash IS. Changes in matrix metalloproteinases and their inhibitors in the tears and blood serum of patients with herpetic keratoconjunctivitis under the influence of antiherpetic antibodies and nimesulide. Pathologia [Internet]. 2021May18 [cited 2024Dec.28];18(1):50-7. Available from: http://pat.zsmu.edu.ua/article/view/220205

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Section

Original research