THE INVESTIGATION OF SOME CYTOKINES ROLE IN THE DEVELOPMENT OF ALOPECIA AREATA

Aljabali M. A., Kuts L. V.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

The immune response plays a leading role in the pathogenesis of alopecia areata which develops by Тh1-type with the formation of a large number of proinflammatory cytokines: IL-1, IL-2, IL-6, IL-8, IFN-γ and TNF-α. The anti-inflammatory cytokines disrupt the excessively formation of them under normal conditions. The Th2-cells produce anti-inflammatory cytokines. The role of Th2 cytokines is not clear with studies showing varied and contradictory results. In recent years, a new type of T-helpers has been discovered – Th-17, producing IL-17A. Th-17 plays a fundamental role in the immunopathogenesis of a wide range of autoimmune diseases. However, the involvement of Th17 in the pathogenesis of alopecia areata is the least studied. Therefore, the aim of our study was to analyze the possible relation between the serum content of T-dependent cytokines (IL-17A, IL-2, IL-10) and the development of alopecia areata. The venous blood of 104 patients with alopecia areata age of (35,7 ± 8,9) years was used in the study. During the patients examination the data on age, sex, smoking, interleukin-17A (pg/ml), interleukin-2 (pg/ml) and interleukin-10 (pg/ml) were obtained. Also, the severity of alopecia tool index was assessed in each subject. To measure the serum level of interleukins in group the Sandwich-ELISA method (Enzyme-linked Immunosorbent Assay) was used. Unpaired two-tailed Student t-test was used for statistical analysis. The significance level was set at P < 0.05. The obtained results revealed that proinflammatory cytokines IL-17A and IL-2 are associated with the emergence of alopecia areata. Thus, it was found that serum levels of IL-17A and IL-2 were increased in patients with alopecia areata. The association of IL-10 with the development of alopecia areata was not established.

alopecia areata, interleukin-17А, interleukin-2, interleukin-10.

1. Alkhalifah A, Alsantali A, Wang E, McElwee KJ, Shapiro J. Alopecia areata update: part I. Clinical picture, histopathology, and pathogenesis. J Am Acad Dermatol. 2010;62:177-88.
2. Seetharam KA. Alopecia areata: an update. Indian J Dermatol Venereol Leprol. 2013;79:563-75.
3. Tembhre MK, Sharma VK. T-helper and regulatory T-cell cytokines in the peripheral blood of patients with active alopecia areata. Br J Dermatol. 2013;169:543-8.
4. Arca E, Musabak U, Akar A, Erbil AH, Tastan HB. Interferon-gamma in alopecia areata. Eur J Dermatol. 2004;14:33-6.
5. Kasumagic-Halilovic E, Prohic A, Karamehic J. Serum concentrations of interferon-gamma (IFN-g) in patients with alopecia areata: correlation with clinical type and duration of the disease. Med arch. 2010;64:212-4.
6. Attia EA, El Shennawy D, Sefin A. Serum Interleukin-4 and Total Immunoglobulin E in Nonatopic Alopecia Areata Patients and HLA-DRB1 Typing. Dermatol Res Pract. 2010;2010:503-87. DOI: 10.1155/2010/503587
7. Giordano CN, Sinha AA. Cytokine pathways and interactions in alopecia areata. Eur J Dermatol. 2013;23:308-18.
8. Barahmani N, Lopez A, Babu D, Hernandez M, Donley SE, Duvic M. Serum T helper 1 cytokine levels are greater in patients with alopecia areata regardless of severity or atopy. Clin Exp Dermatol. 2010;35:409-16.
9. Cerbina IM. Czitokinoposredovannye mekhanizmy formirovaniya gnezdnoj alopeczii. Nauchnye vedomosti. Seriya Mediczina. Farmacziya. 2014;24(195)28:50-4. [in Russiаn].
10. Kologrivova IV, Kologrivova EN, Suslova TE. Molekulyarnye aspekty funkczionirovaniya T-khelperov 17-go tipa. Byulleten Sibirskoj medicziny. 2011;11:93-9. [in Russian].
11. Bettelli E, Korn T, Vijay K. Th17: the third member of effector T cell Trilogy. Immunol. 2007;19:652-7.
12. Tabarkiewicz J, Pogoda K, Karczmarczyk A, Pozarowski P, Giannopoulos K. The Role of IL-17 and Th17 Lymphocytes in Autoimmune Diseases. Arch Immunol Ther Exp (Warsz). 2015;63:435-49.
13. Atwa MA, Youssef N, Bayoumy NM. T-helper 17 cytokines (interleukins 17, 21, 22, and 6, and tumor necrosis factor-alpha) in patients with alopecia areata: association with clinical type and se- verity. Int J Dermatol. 2016;55(6):666-72. Available from: https://doi.org/10.1111/ ijd.12808
14. El-Morsy EH, Eid AA, Ghoneim H, Al-Tameemi KA. Serum level of interleukin-17A in patients with alopecia areata and its relationship to age. Int J Dermatol. 2015;55(8):869-74.
15. Bilgic O, Sivrikaya A, Unlu A, Altinyazar HC. Serum cytokine and chemokine profiles in patients with alopecia areata. J Dermatolog Treat. 2016;27:260-3.
16. Han YM, Sheng YY, Xu F, Qi SS, Liu XJ, Hu RM, et al. Imbalance of T-helper 17 and regulatory T cells in patients with alopecia areata, J.25. Dermatol. 2015;42:981-8. DOI: 10.1111/1346-8138.12978
17. Tanemura A, Oiso N, Nakano M, Itoi S, Kawada A, Katayama I. Alopecia areata: Infiltration of Th17 cells in the dermis, particularly around hair follicles. Dermatology. 2013;226:333-6. DOI: 10.1159/000350933
18. Olsen E, Hordinsky M, McDonald-Hull S, Price V, Roberts J, Shapiro J, Stenn K. Alopecia areata investigational assessment guidelines. National Alopecia Areata Foundation. J Am Acad Dermatol. 1999;40:242-6.
19. Rossi A, Muscianese M, Piraccini BM. Italian Guidelines in diagnosis and treatment of alopecia areata. Giornale Italiano di Dermatologia e Venereologia. 2019;154(6):609-23. DOI: 10.23736/S0392-0488.19.06458-7
20. Messenger AG, McKillop J, Farrant P, McDonagh AJ, Sladden M. British Association of Dermatologists’ guidelines for the management of alopecia areata. British Journal of Dermatology. 2012;166:916-26.
21. Olsen EA, Hordinsky M, McDonald-Hull S, Price V, Roberts J, Shapiro J, et al. Alopecia areata investigational assessment guidelinese – Part II. J Am Acad Dermatol. 1999;40:242-6.
22. Olsen EА, Hordinsky MK, Price VН, Roberts JL, Shapiro J, Canfield D, et al. Alopecia areata investigational assessment guidelinese. Part II. J. Am. Acad. Dermatol. 2004;51:448-51.
23. McElwee KJ, Boggess D, King LE Jr, Sundberg JP. Experimental induction of alopecia areata-like hair loss in C3H/HeJ mice using fullthickness skin grafts. J Invest Dermatol. 1998;111:797-803.
24. Freyschmidt-Paul P, Happle R, Kissling S, Wenzel E, Sundberg JP, Zöller M, Hoffmann R. Interleukin-10-deficient mice are less susceptible to the induction of alopecia areata. J Invest Dermatol. 2002;119:980-2.
25. Teraki Y, Imanishi K, Shiohara T. Cytokines in alopecia areata: contrasting cytokine profiles in localized form and extensive form (alopecia universalis). Acta Derm Venereol. 1996;76:421-3.
26. Gautam RK, Singh Y, Gupta A, Arora P, Khurana A, Chitkara A. The profile of cytokines (IL-2, IFN-γ, IL-4, IL-10, IL-17A, and IL-23) in active alopecia areata. J Cosmet Dermatol. 2020;19:234-40. DOI: 10.1111/jocd.12970
27. Barahmani N, Lopez A, Babu D, Hernandez M, Donley SE, Duvic M. Serum T helper 1 cytokine levels are greater in patients with alopecia areata regardless of severity or atopy. Clin Exp Dermatol. 2010;35:409-16.
28. Cua DJ, Tato CM. Innate IL-17 producing cells: the sentinels of the immune system. Nat Rev. 2010;10:479-89.

«Bulletin of problems biology and medicine» Issue 4 (158), 2020 year, 93-96 pages, index UDK 616.58- 616.59-616.594-616.594.1-616.594.12-3

10.29254/2077-4214-2020-4-158-93-96