The role of melatonin in reducing the cytokines IL-6 and IL-17 in menopause




Melatonin; Inflammatory Mediators; Menopause; Inflammatory Modulation; IL-6; IL-17.


Menopause is a biological process that happens in women, since the ovaries stop producing hormones due to the lack of eggs. This stage of a women’s life can happen at 35 to 60 years, and might cause uncomfortable symptoms and even diseases, worsening the life quality of women. The cessation of ovulation has the consequence of reducing the production of estradiol that causes a change in the immune system, predisposing to inflammatory and infectious diseases. Such predisposition can increase the inflammatory mediators IL-6 and IL-17 in the female organism. Melatonin is a hormone manufactured by the pineal gland at night, since the light can debug the hormone. This hormone regulates the circadian rhythm and an immunomodulator. This immunomodulating function that melatonin has can mediate the synthesis and inhibition of some inflammatory mediators. This review aims to identify if melatonin treatment can reduce the quantity of inflammatory mediators in menopausal women. This analysis was performed through a review, with papers searched in the PubMed, Scielo, ScienceDirect and RBAC databases using the keywords: melatonin, menopause, inflammatory mediator, inflammatory modulation, published in the last 15 years. Analyzing the articles, it was identified that melatonin influences the decrease of inflammatory mediators, which may help to improve the life quality of women that are or will be in menopause. However, it is necessary to search for protocols for the use of melatonin, with prediction of use doses and verification of the effects on the body.


Acunã-Castrovijo, D., Escames, G., Venegas, C., Díaz-Casado, M. E., Lima-Cabello, E. & López, L. C. (2014). Extrapineal melatonin: sources, regulation, and potencial functions. Cellular and Molecular Life Sciences, 71(16), 2997-3025.

Arendt, J. (2005). Melatonin: characteristics, concerns and prospects. Journal of Biological Rhythms, 20(4), 291-303.

Armijo, P. R., Reginato, R. D., Maganhin, C. C., Fuchs, L. F. P., Simões, R. S., Baracat, E. C., & Júnior, J. M. S. (2013). Ação da melatonina no tecido cartilaginoso. Sociedade Brasileira de Reprodução Humana, 28(1), 24-29.

Besedovsky, L., Lange, T., & Born, J. (2011). Sleep and immune function. European Journal of Physiology, 463(1). 121-137.

Carrillo-Vico, A., Lardone, P. J., Alvarez-Sanchez, N., Rodriguez, A., & Guerrero, J. M. (2013). Melatonin: Buffering the immune system. International Journal of molecular Sciences, 14(4), 8638-8683.

Cavadas, L. F., Nunes, A., Pinheiro, M., & Silva, P. T. (2010). Abordagem da menopausa nos cuidados de saúde primários. Acta Médica Portuguesa, 23(2), 227-236.

Cruz-Machado, S. S., Pinato, L., Tamura, E. K., Carvalhosous, C. E., & Markus, R. P. (2012). Glia-pinealocyte network: the paracrine modulation of melatonin synthesis by tumor necrosis factor (TNF). PLOS ONE, 7(7), 40142.

Dubocovich, M. L, & Markowska, M. (2005). Functional MT1 and MT2 melatonin receptors in mammals. Endocrine, 27(2), 101-110.

Estrela, C. (2018). Metodologia Científica: Ciência, Ensino, Pesquisa. Editora Artes Médicas.

Faria, M. A., Simões, R. S., Santos, M. A., Junior, J. M. S., & Carbonel, A. A. F. (2013). Pós-menopausa e sistema imune. Reprodução e Climatério, 28(1), 30-35.

Favero, G., Franceschietti, L., Bonomini, F., Rodella, L. F., & Rezzani, R. (2017). Melatonin as na anti-inflammatory agent modulating inflammasome activation. International Journal of Endocrinology, 1-13.

Freitas, C. R. P., Terra, K. L., & Mercês, N. N. A. (2011). Conhecimentos dos acadêmicos sobre prevenção do câncer de mama. Revista Gaúcha de Enfermagem, 32, 4.

Gameiro, C. M., Romão, F., & Castelo-Branco, C. (2010). Menopause and aging: Changes in the immune system – A review. Maturitas, 67(4), 316-320.

Hardeland, R. (2018). Melatonin and inflammation – Story of a double-edged blade. Journal of Pineal Research, e12525.

Hardeland, R. (2014). Melatonin and circadian oscillators in aging – A dynamic approach to the multiply connected players. Aging and Health – A Systems Biology Perspective, 128-140.

Itaborahy, R. M. R., & Medeiros, S. F. (2016). Influence of estrogen therapy on immune markers in postmenopausal women. Climacteric, 19(5), 496-500.

Jehan, S., Jean-Louis, G., Zizi, F., Auguste, E., Pandi-Perumal, S. R., Gupta, R. … Brzezinski, A. (2017). Sleep, melatonin, and the menopausal transition: What are the links? Sleep Science, 10(1), 11-18.

Jockers, R., Delagrange, P., Dubocovich, M. L., Markus, R. P., Renault, N., Tosini, G. … Zlotos, D. P. (2016). Update on melatonin receptors: IUPHAR review 20. British Journal of Pharmacology, 173(18), 2702-2725.

Kireev, R. A., Vara, E., Vinã, J., & Tresguerres, J. A. F. (2014). Melatonin and estrogen treatments were able to improve neuroinflammation and apoptotic processes in dentate gyrus of old ovariectomized female rats. Journal of the American Aging Association, 36(5), 9707.

Kireev, R., Tresguerres, A. C. F., Garcia, C., Ariznavarreta, C., Vara, E., & Tresguerres, J. A. F. (2008). Melatonin is able to prevent the liver of old castrated female rats from oxidative and pro-inflammatory damage. Journal of Pineal Research, 45(4), 394-402.

Korn, T., Bettelli, E., Oukka, M., & Kuchroo, V.K. (2009). IL-17 and Th17 cells. Annual Review of Immunology, 27, 485-517.

Kuwabara, T., Ishikawa, F., Kondo, M., & Kakiuchi, T. (2017). The role of IL-17 and related cytokines in inflammatory autoimmune diseases. Mediators of Inflammation, 1-11.

Lee, J .S., & Cua, D. J. (2015). Melatonin lulling Th17 cells to sleep. Elsevier Inc, 162(6), 1212-1214.

Li, M. Y., Pan, S. R., & Qiu, A. Y. (2016). Roles of microRNA-221/222 in type 2 diabetic patients with post-menopausal breast cancer. Genetics and Molecular Research, 15(2).

Luchetti, F., Canonico, B., Betti, H., Arcangeletti, H., Pilolli, F., Piroddi, H. … Galli, F. (2010). Melatonin signaling and cell protection function. The FASEB Journal, 24(10), 3603-3624.

Maganhin, C. C., Carbonel, A. A. F., Hatty, J. H., Fuchs, L. F. P., Oliveira-Junior, I. S., Simões, M. J. … Soares-Junior, J. M. (2008). Efeitos da melatonina no sistema genital feminino: Breve revisão. Revista da Associação Médica Brasileira, 54(3), 267-271.

Markus, R. P., Ferreira, Z. S., Fernandes, P. A., & Cecon, E. (2007). The immune-pineal axis: a shuttle between endocrine and paracrine melatonin sources. Neuroimmunomodulation, 14(3-4), 126-133.

Medeiros, S. F., Maitelli, A., & Nince, A. P. B. (2007). Efeitos da terapia hormonal na menopausa sobre o sistema imune. Revista Brasileira de Ginecologia e Obstetrícia, 29, 593-601.

Ministério da saúde. (2008). Manual de atenção à mulher no climatério/menopausa. Secretaria de Atenção à Saúde, caderno: 9.

Neto, J. A. S., & Scaldaferri, P. M. (2004). Melatonina e câncer: revisão de literatura. Revista Brasileira de Cancerologia, 51(1), 49-58.

Oliveira, J., Peruch, M. H., Gonçalves, S., & Haas, P. (2016). Female hormone pattern: menopause and replacement therapy. Brazilian Journal of Epilepsy and Clinical Neurophysiology, 48(3), 198-210.

Pedro, A. O., Neto, A. M. P., Paiva, L. H. S. C., Osis, M. J., & Hardy, E. (2003). Idade de ocorrência da menopausa natural em mulheres brasileiras: resultados de um inquérito populacional domiciliar. Caderno de Saúde Pública, 19(1).

Reiter, R. J., Rosales-Corral, S. A., & Tan, D. X. (2013). Peripheral reproductive organ health and melatonin: ready for prime time. International Journal of Molecular Sciences, 14(4), 7231-7272.

Reiter, R. J., Tan, D. X., & Fuentes-Broto, L. (2010). Melatonin: a multitasking molecule. Neuroendocrinology: The Normal Neuroendocrine System, 181, 127-151.

Ren, W., Liu, G., Chen, S., Yin, J., Wang, J., Tan, B. … Yin, Y. (2016). Melatonin signaling in T cells: functions and applications. Journal of Pineal Research, 62(3), 12394.

Rocha, M. D. H. A., & Rocha, P. A. (2010). Do climatério à menopausa. Revista Cientifica do ITPAC, 3, 1, 24-27.

Sapir-Koren, R., & Livshits, G. (2017). Postmenopausal osteoporosis in rheumatoid arthritis: The estrogen deficiency-immune mechanisms link. Bone, 103, 102-115.

Slominski, R. M., Reiter, R. J., Schlabritz-Loutsevitch, N., Ostrom, R. S., & Slominski, A. T. (2012). Melatonin membrane receptors in peripheral tissues: Distribution and functions. Molecular and Cellular Endocrinology, 351(2), 152-166.

Tortora, G. J., & Derrickson, B. (2012). Princípios de anatomia e fisiologia. ed. 12, 1228, Rio de Janeiro: Guanabara Koogan.

Vielma, J. R., Bonilla, E., Chancín-Bonilla, L., Medina-Leendertz, S., & Bravo, Y. (2014). Effects of melatonin on oxidative stress, and resistance to bacterial, parasitic, and viral infections: a review. Acta Tropica, 137, 31-38.

Who. (2010). Research on the menopause in the 1990s. World Health Organization.

Xia, M. Z., Liang, Y. I., Wang, H., Zhang, Z. H., Chen, Y. H., Zhang, C. … Song, L. H. (2012). Melatonin modulates TLR4-mediated inflammatory genes through myD88- and TRIF-dependent signaling pathways in lipopolysaccharide-stimulated RAW264.7 cells. Journal of Pineal Research, 53(4), 325-334.

Yasui, T., Uemura, H., Yamada, M., Matsuzaki, T., Tsuchiya, N., Noguchi, M., & Irahara, M. (2008). Associations of interleukin-6 with interleukin-1β, interleukin-8 and macrophage inflammatory protein-1β in midlife women. Cytokine, 41(3), 302-306.

Zarazadeh, M., Khorshidi, M., Emami, M., Janmohammadi, P., Kord-Varkaneh, H., Mousavi, S. M. … Alizadeh, S. (2019). Melatonin supplementation and pro-inflammatory mediators: a systematic review and meta-analysis of clinical trials. European Journal of Nutrition, 59(5), 1803-1813.

Zhang, J., Fu, Q., Ren, Z., Wang, Y., Wang, C., & Shen, T. (2014). Changes of serum cytokines related Th1/Th2/Th17 concentration in patients with postmenopausal osteoporosis. Gynecological Endocrinology, 31(3), 183-190.



How to Cite

CORREA, R. F.; CASAGRANDE, T. A. C. The role of melatonin in reducing the cytokines IL-6 and IL-17 in menopause. Research, Society and Development, [S. l.], v. 10, n. 12, p. e63101220074, 2021. DOI: 10.33448/rsd-v10i12.20074. Disponível em: Acesso em: 20 feb. 2024.



Health Sciences