Serum Level of IL-6, Reactive Oxygen Species and Cortisol in Patients with Recurrent Aphthous Stomatitis related Imbalance Nutrition Intake and Atopy


  • Nanan Nur'aeny Medical Sciences Doctoral Program, Faculty of Medicine, Universitas Padjadjaran, Jalan Professor Eyckman No.38, Bandung 40161, Jawa Barat
  • Dida Akhmad Gurnida Department of Child Health, Faculty of Medicine, Universitas Padjadjaran/Dr. Hasan Sadikin General Hospital, Jalan Professor Eyckman No.38, Bandung 40161, Jawa Barat
  • Oki Suwarsa Department of Dermatology and Venereology, Faculty of Medicine, Universitas Padjadjaran/Dr. Hasan Sadikin General Hospital, Jalan Professor Eyckman No.38, Bandung 40161, Jawa Barat
  • Irna Sufiawati Department of Oral Medicine, Faculty of Dentistry, Universitas Padjadjaran/Dental Hospital, Jalan Sekeloa Selatan No.1, Bandung 40132, Jawa Barat



atopy, cortisol, IL-6, malnutrition, recurrent aphthous stomatitis, ROS


One of the most common oral ulcerations is recurrent aphthous stomatitis (RAS), affecting approximately 20% of the general population worldwide. The etiology of RAS is still unclear but it is considered to be multifactorial, including imbalanced nutrition intake and allergic conditions such as atopy. The purpose of this study was to investigate the differences and correlation between the serum level of IL-6, reactive oxygen species (ROS), and cortisol in RAS patients. Our study was cross-sectional and used a consecutive sampling method. There were significant differences of IL-6 and ROS levels in all groups (p = 0.000, p = 0.049 respectively) and a significant correlation between cortisol and ROS in the RAS group without atopy (r = -0.985, p = 0.015). Serum IL-6 and ROS measurement may be used for detecting RAS caused by malnutrition or atopy but not cortisol for patients without psychological stress detected. This is consistent with the results of a very strong correlation with a negative value between cortisol and ROS in RAS without atopy.


Greenberg, M.S., Glick, M. & Ship, J.A., Burket's Oral Medicine, Ed. 12. People's Medical Publishing House, Connecticut, 2015.

Wu, Y.C., Wu, Y.H., Wang, Y.P., Chang, J.Y.F., Chen, H.M. & Sun, A,, Hematinic Deficiencies and Anemia Statuses in Recurrent Aphthous Stomatitis Patients With or Without Atrophic Glossitis, J. Formos. Med. Assoc., 115(12), pp. 1061-1068, 2016.

Chavan, M., Jain, H., Diwan, N., Khedkar, S., Shete, A. & Durkar, S., Recurrent Aphthous Stomatitis: A Review, J. Oral Pathol. Med., pp. 1-8, 2012.

Fornasa, C.V. & Gallina, P., Expression of Pathergy in Atopics, Acta Dermatoven APA, 15 (3), pp. 144-147, 2006.

Bao, Z., Shi, J., Yang, X. & Liu, L., Hematinic Deficiencies in Patients with Recurrent Aphthous Stomatitis: Variations by Gender and Age, Med. Oral Patol. Oral Cir. Bucal., 23(2), pp. e161-7, 2018.

Fornasa, C.V., Bezze, G., Rosin, S., Lazzaro, M., Tarantello, M. & Cipriani, R., Recurrent Aphthous Stomatitis and Atopy, Acta Derm. Venereol., 83(6), pp. 469-470, 2003.

Nur'aeny, N., Sari, E.F., & Sutedja, E., Correlation between Oral Lesions and Total Serum Ige Level in Atopic Patients, 9th International Dental Federation-Indonesia Dental Association Joint Meeting, pp. 41, 2013.

Challacombe, S.J., Alsahaf, S. & Tappuni, A., Recurrent Aphthous Stomatitis: Towards Evidence-Based Treatment?, Curr. Oral Heal. Reports, 2(3), pp. 158-167, 2015.

Yao, X., Cai, L. & Yang, F., Clinical Analysis of Yinzhi Decoction Combined with Compound Gargle Solution Chlorhexidine Giuconatie in the Treatment of Recurrent Aphthous Ulcer and Its Effect on Immune Function and Inflammatory Factors in Patients, Int. J. Clin. Exp. Med., 11(9), pp. 10002-10008, 2018.

Jones, S.A., Takeuchi, T., Aletaha, D., Smolen, J., Choy, E.H. & McInnes, I., Interleukin 6: The Biology Behind The Therapy, Considerations Med., 2(1), pp. 2-6, 2018.

Bankvall, M., Recurrent Aphthous Stomatitis, Ineko AB, Gothenburg, 2017.

Sardaro, N., Vella, F.D., Incalza, M.A., Stasio, D.D.I., Lucchese, A. & Contaldo, M., Oxidative Stress and Oral Mucosal Diseases: An Overview, 296, pp. 289-296, 2019.

Zhang, Z., Zhang, Q., Xue, Y., Chen, G., Wu, Z. & Fang, H., Serum Levels of Total Antioxidant Status, Nitric Oxide and Nitric Oxide Synthase in Minor Recurrent Aphthous Stomatitis Patients, Medicine., 98(3), pp. 1-4, 2019.

Arikan, S., Durusoy, C., Akalin, N., Haberal, A. & Seckin, D., Oxidant/Antioxidant Status in Recurrent Aphthous Stomatitis, Oral Dis., 15(7), pp. 512-515, 2009.

Gallo, C.D.B., Angela, I.M., Mimura, M., Norberto, I.I. & Sugaya, N., Psychological Stress and Recurrent Aphthous Stomatitis, Clinics, 64(6), pp. 645-648, 2009.

Bilal, N., An Assessment of the Levels of Anxiety and Depression in Patients with Recurrent Aphthous Stomatitis, Arch. Otolaryngol. Rhinol., 2, pp. 001-005, 2016.

Farmaki E.A., Poulopoulos, A.K., Evipatianos, A., Farmakis, K., Karamouzis, M. & Antoniades D., Increased Anxiety Level and High Salivary and Serum Cortisol Concentrations in Patients with Recurrent Aphthous Stomatitis, Tohoku J. Exp. Med., 214 (4), pp. 291-296, 2008.

Srivastava, K.K., Kumar, R., Stress, Oxidative Injury and Disease, Indian J. Clin. Biochem., 30(1), pp. 3-10, 2015.

Queiroz, S.I.M.L., de Medeiros, A.M.C, Gurgel, B.C.V., da Silva, M.V.A., de Oliveira, P.T., da Silveiram, .J.D., Recurrent Aphthous Ulceration: An Epidemiological Study of Etiological Factors, Treatment and Differential Diagnosis, An Bras Dermatol., 93(3), pp. 341-346, 2018.

Akintoye, S.O. & Greenberg, M.S., Recurrent Aphthous Stomatitis, Dent. Clin. North Am., 58(2), pp. 281-97, 2015.

Fauzi, F., Sudiro, M. & Lestari, B.W., Prevalence of Allergic Rhinitis based on World Health Organization (ARIA-WHO) Questionnaire Among Batch 2010 Students of the Faculty of Medicine Universitas Padjadjaran, Althea Med. J., 2(4), pp. 620-625, 2015.

Knig, K., Klemens, C., Eder, K., Nicolo, M.S., Becker, S., Kramer, M.F. & Grger, M., Cytokine Profiles in Nasal Fluid of Patients with Seasonal or Persistent Allergic Rhinitis, Allergy, Asthma Clin. Immunol., 11(26), pp. 1-10, 2015.

Maheswaran, T., Yamunadevi, A., Ilayaraja, V., Institutions, V.E., & Dineshshankar, J., Correlation Between the Menstrual Cycle and the Onset of Recurrent Aphthous Stomatitis, J. Indian Acad. Dent. Spec. Res., 2(1), pp. 25-26, 2015.

Mccartan, B.E. & Sullivan, A., Variations in the Course of Recurrent Aphthous Stomatitis in Women Taking Hormone Replacement Therapy or Oral Contraceptives, J. Eur. Acad. Dermatology Venereol., 6(0926), pp. 32-34, 1996.

Keenan, A.V. & Spivakovksy, S., Stress Associated with Onset of Recurrent Aphthous Stomatitis, Nat. Publ. Gr., 14(1), pp. 25, 2013.

Polat, C., Duzer, S., Ayynldiz, H., Sec, S., Aksoy, N., Sakallioglu, O., AkyiAYit, A. & etiner, H., Association Between Anxiety, Depression, and Salivary Cortisol Levels in Patients with Recurrent Aphthous Stomatitis, Turk Otolarengoloji Arsivi/Turkish Arch. Otolaryngol., 56(3), pp. 166-169, 2018.

Barrett, K., Brooks, H., Boitano, S. & Barman, S., Ganong's Review of Medical Physiology, Ed 23, Mc Graw Hill Medical, Toronto, 2010.

Sharma, R.K. & Agarwal, A., Role of Reactive Oxygen Species in Gynecologic Diseases, Reprod. Med. Biol., 3(4), pp. 177-199, 2004.

Shkolnik, K., Tadmor, A., Dor, S.B., Nevo, N., Galiani, D. & Dekel N., Reactive Oxygen Species are Indispensable in Ovulation, Proc. Natl. Acad. Sci. USA, 108(4), p. 1462-1467, 2011.

Nur'aeny, N., Sufiawati, I., Suwarsa, O. & Gurnida, D.A., Serum IL-6 Levels of Atopic Patients with Recurrent Aphthous Stomatitis (RAS), Padjadjaran J. Dent., 31(1), pp. 20-24, 2019.

Bazrafshani, M.R., Hajeer, A.H., Ollier, W.E.R. & Thornhill, M.H., IL-1B and IL-6 Gene Polymorphisms Encode Significant Risk for the Development of Recurrent Aphthous Stomatitis (RAS), Genes Immun., 3(5), pp. 302-305, 2002.

Nibali, L., Fedele, S., D'Aiuto, F. & Donos, N., Interleukin-6 in Oral Diseases: A Review, Oral Dis., 18(3), pp. 236-243, 2012.

Yang Y, Wang, Q., Song, X., Jiang, W., Tang, S., Shen, F. & Xie, S., Association between IL-4, IL-6, IL-18 Polimorphisms and Atopic Dermatitis Risk: A Meta-analysis, Int. J. Clin. Exp. Med., 10(5), pp. 7375-7386, 2017.

Liu, Z., Ren, Z., Zhang, J., Chuang, C.C., Kandaswamy, E., Zhou, T. & Zuo, L., Role of ROS and Nutritional Antioxidants in Human Diseases, Front. Physiol., 9, pp. 1-14, 2018.

World Health Organization, Haemoglobin Concentrations for the Diagnosis of Anaemia and Assessment of Severity, in VMNIS | Vitamin and Mineral Nutrition Information System, pp. 1-6, 2011.

Roe, M., Church, S., Pinchen, H. & Finglas, P., Nutrient Analysis of Fruit and Vegetables, Department of Health, Norwich, 2013.

Neerven, R.J.J.V. & Savelkoul, H., Nutrition and Allergic Diseases, Nutrients, 9(7), pp. 1-8, 2017.

Nutten, S., Atopic Dermatitis: Global Epidemiology and Risk Factors,, Ann. Nutr. Metab.., 66(supp 1), pp. 8-16, 2015.

Ji, H. & Li, X.K, Oxidative Stress in Atopic Dermatitis, Oxidative Medicine and Cellular Longevity, pp. 1-8, 2016.

Shi, Q., Lei, Z., Cheng, G., Li, D., Wang, Q., Luo, S., Yang, H. & Jia, H. Mitochondrial ROS Activate Interleukin-1 Expression in Allergic Rhinitis, Oncol. Lett., 16(3), pp. 3193-3200, 2018.

Cho, Y.S. & Moon, H.B., The Role of Oxidative Stress in the Pathogenesis of Asthma, Allergy Asthma Immunol Res., 2(3), pp. 183-187, 2010.

Avci, E., Akarslan, Z.Z. & Erten, H. & Cevher, S.C., Oxidative Stress and Cellular Immunity in Patients with Recurrent Aphthous Ulcers, Braz. J. Med. Biol. Res., 47(5), pp. 355-360, 2014.