, Volume 30, Issue 2, pp 175–183 | Cite as

The effects of royal jelly on autoimmunity in Graves' disease

  • Cihangir Erem
  • Orhan Deger
  • Ercüment Ovali
  • Yasam Barlak
Original Articles



Graves' disease is an organ-specific autoimmune disease with unknown etiology. TSHR Ab plays the most important role for the pathogenesis of Graves' disease. Recently, the role of cytokines for the pathogenesis of Graves' disease has been studied extensively. Royal jelly (RJ) is a creamy product secreted by young nurse worker bees (Apis mellifera), and it is synthesized in the hypopharyngeal and mandibular glands. RJ has been reported to have such pharmacological characteristics as antitumor, antibacterial, antihypercholesterolemic, antiallergic, antiinflammatory, and immunomodulatory properties. The major aim of the present study is to evaluate the effect of RJ on autoimmunity in peripheral lymphocyte culture and to establish the therapeutic doses.

Research Design and Methods

In the first phase, lymphocyte cell isolation from four voluntary healthy subjects was performed to find the effective concentration of RJ on immunity. Serial dilutions of the RJ were prepared (0–5 mg/mL). All isolated lymphocyte cells were treated with the above diluted samples. MTT test was carried out after incubation of 72 h. In the second phase, six patients with Graves' disease, newly diagnosed by clinical and laboratory methods and admitted to my hospital and untreated were identified. RJ samples of 0 and 4 mg/mL were incubated in a culture medium for 72 h with isolated lymphocytes obtained from the patients. After incubation, MTT test in lymphocyte cell culture, Th1 cytokines IFN-γ, TNF-α, and Il-12, and Th2 cytokines IL-4 and Il-10 levels by the enzyme amplified sensitivity immunoassay (EASIA) method and TSHR Ab by the radioreceptor method were determined.


The concentration causing lymphocytes to proliferate was found to be 4 mg/mL by MTT test after incubation of 72 h in cell culture medium. Of the cytokines produced and secreted from lymphocytes, IFN-γ increased, whereas, other cytokines decreased in RJ concentration of 4 mg/mL. Significant differences were found only for IFN-γ and TNF-α. IL-4 concentrations were kept near the level of significancy. Of Th1/Th2 ratios, IFN-γ/IL-4 and IFN-γ/IL-10 ratios also exhibited significant differences between 0 and 4 mg/mL. RJ treatment in lymphocytes from patients with Graves' disease shifted the Th1/Th2 cytokine ratio to the side of Th1 cytokine. Therefore, RJ using the treatment and establishing a remission of Graves' disease may be effective as an antithyroid drug treatment. TSHR Ab levels of lymphocyte cell culture supernatants treated with RJ showed significant decreases. Also, the result may suggest that RJ may exert an effect similar to an antithyroid drug for decreasing TSHR Ab levels.


RJ may be effective as an immunomodulatory agent in Graves' disease.

Key Words

Autoimmunity Graves' disease lymphocyte cell culture royal jelly cytokines 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Jones, B. M., Kwok, C. C. H., and Kung, A. W. C. (1999). J. Clin. Endocrinol. Metab. 84, 4106–4110.PubMedCrossRefGoogle Scholar
  2. 2.
    Davies T. F. (2000) Graves' disease. In: Werner and Igbar's the thyroid. 8th ed Braverman, L. E. and Utiger, R. D. (eds.). Lippincott-Raven: Philadelphia, pp. 518–555.Google Scholar
  3. 3.
    Itoh, M., Uchimura, K., Makino, M., et al. (2000). Cytokine 12, 688–693.PubMedCrossRefGoogle Scholar
  4. 4.
    Ajjan, R. A. and Weetman, A. P. (2003). Autoimmunity 36, 351–359.PubMedCrossRefGoogle Scholar
  5. 5.
    Ward, L. S. and Fernandes, G. A. (2000). Braz. J. Med. Res. 33, 65–69.Google Scholar
  6. 6.
    Mosmann, T. R., Cherwinski, H., Bond, M. W., Giedlin, M. A., and Coffman, R. L. (1986). J. Immunol. 136, 2348–2357.PubMedGoogle Scholar
  7. 7.
    Weetman, A. P. (2004). Clin. Endocrinol. 61, 405–413.CrossRefGoogle Scholar
  8. 8.
    Swain, S. L., Weinberg, A. D., English, M., and Huston, G., (1990). J. Immunol. 145, 3796–3806.PubMedGoogle Scholar
  9. 9.
    Cooper, D. S. (2000). In: Werner and Igbar's the thyroid. 8th ed. Braverman, L. E. and Utiger, R. D. (eds.) Lippincott-Raven Philadelphia, pp. 691–715.Google Scholar
  10. 10.
    Teng, C. S. and Yeung, R. T. (1980). J. Clin. Endocrinol. Metab. 50, 144–147.PubMedGoogle Scholar
  11. 11.
    McGregor, A. M., Petersen, M. M., McLachlan, S. M., Rooke, P., Smith, B. R., and Hall, R. (1980). N. Engl. J. Med. 303, 302–307.PubMedCrossRefGoogle Scholar
  12. 12.
    Weetman, A. P., McGregor, A. M., and Hall, R. (1983). Clin. Immunol. Immunopathol. 28, 39–45.PubMedCrossRefGoogle Scholar
  13. 13.
    Piana, L., Manzi, L., and Krell, R. (1996) Royal jelly.http/www. (last accessed October 2006).Google Scholar
  14. 14.
    Sver, L., Orsolic, N., Tadic, Z., Nijari, B., Valpotic, I., and Basic, I. (1996). Comp. Immunol. Microbiol. Infect. Dis. 19, 31–38.PubMedCrossRefGoogle Scholar
  15. 15.
    Oka, H., Emori, Y., Kobayashi, N., Hayashi, H., and Nomoto, K. (2001). Int. Immunopharmacol. 1, 521–532.PubMedCrossRefGoogle Scholar
  16. 16.
    Sauerwald, N., Polster, J., Bengsch, E., Niessen, L., and Vogel, R. F. (1998). Adv. Food Sci. 20, 46–52.Google Scholar
  17. 17.
    Nagai, T., Sakai, M., Inoue, R., Inoue, H., and Suzuki, N. (2001). Food Chem. 75, 237–240.CrossRefGoogle Scholar
  18. 18.
    Okuda, H., Kameda, K., Morimoto, C., Matsuura, Y., Chiaki, M., and Jiang, M. (1998). Honeybee Science 19, 9–14.Google Scholar
  19. 19.
    Tamura, T., Fuji, A., and Kuboyama, N. (1987). Folia. Pharmacol. Japon [in Japanase] 89, 73–80.CrossRefGoogle Scholar
  20. 20.
    Shinodo, M., Nakajin, S., Oikawa, T., Sato, K., Kamogawa, A., and Akiyama, Y. (1978). Yakugaku Zasshi [in Japanase] 98, 139–145.Google Scholar
  21. 21.
    Vittek, J. (1995). Experientia 51, 927–935.PubMedCrossRefGoogle Scholar
  22. 22.
    Tokunaga, K.-H., Yoshida, C., Suzuki, K.-M., et al., (2004). Biol. Pharm. Bull. 27, 189–192.PubMedCrossRefGoogle Scholar
  23. 23.
    Kataoka, M., Arai, N., Taniguchi, Y., et al., (2001). Natural Medicines [in Japanase] 55, 174–180.Google Scholar
  24. 24.
    Kamakura, M., Mitani, N., Fukuda, T., and Fukushima, M. (2001). J. Nutr. Sci. Vitaminol. 47, 394–401.PubMedGoogle Scholar
  25. 25.
    Fujii, A., Kobayashi, S., Kuboyama, N., et al., (1990). Jpn. J. Pharmacol. 53, 331–337.PubMedGoogle Scholar
  26. 26.
    Emori, Y., Oka, H., Ohya, O., Tamaki, H., and Hayashi, H. (1998). Biotherapy (Jpn.) 12, 313–319.Google Scholar
  27. 27.
    Emori, Y., Oka, H., Ohya, O., Tamaki, H., Hayashi, H., and Nomoto, K. (1998). Biotherapy (Jpn.) 12, 1143–1148.Google Scholar
  28. 28.
    Emori, Y., Oka, H., Kobayashi, Y., Ohya, O., Tamaki, H., and Hayashi, H. (1999). Biotherapy (Jpn.) 13, 281–287.Google Scholar
  29. 29.
    Majtan, J., Kovacova, E., Bilikova, K., and Simuth, J. (2006). Int. Immunopharmacol. 6, 269–278.PubMedCrossRefGoogle Scholar
  30. 30.
    Xie, J., Liu, G. and Liu, K. (1990). Zhongguo Yaoke Daxue Xuebao 21, 167–169.Google Scholar
  31. 31.
    Liu, L. S., Xiao, X. M., and Ziheng, R. C. (1984). Chung Hua Fang She I Hsueh Yu Fang Hu Tsa Chih 4, 25–26.Google Scholar
  32. 32.
    Kohno, K., Okamoto, I., Sano, O., et al., (2004). Biosci. Biotechnol. Biochem. 68, 138–145.PubMedCrossRefGoogle Scholar
  33. 33.
    Simuth, J., Bilikova, K., Kovacova, E., Kuzmova, Z., and Schroder, W. (2004). J. Agric. Food Chem. 52, 2154–2158.PubMedCrossRefGoogle Scholar
  34. 34.
    Koya-Miyata, S., Okamoto, I., Ushio, S., Iwaki, K., Ikeda, M., and Kurimoto, M. (2004). Biosci. Biotechnol. Biochem. 68, 767–773.PubMedCrossRefGoogle Scholar
  35. 35.
    Okamoto, I., Taniguchi, Y., Kunikata, T., et al., (2003). Life Sci. 73, 2029–2045.PubMedCrossRefGoogle Scholar
  36. 36.
    Pollard, J. M. and Walker, J. M. (1997). Basic cell culture protocols. 2nd ed. Humana Press: Totowa, NJ.Google Scholar
  37. 37.
    Carmichael, J., DeGraff, W. G., Gazdar, A. F., Mina, J. D., and Mitchel, J. B. (1987). Cancer Res. 47, 936–942.PubMedGoogle Scholar
  38. 38.
    Kamakura, M., Suenobu, N., and Fukushima, M. (2001). Biochem. Biophys. Res. Commun. 282, 865–874.PubMedCrossRefGoogle Scholar
  39. 39.
    Al-Humaidi, M. A. (2000). Saudi Med. J. 21, 639–644.PubMedGoogle Scholar
  40. 40.
    Kocjan, T., Wraber, B., Repnik, U., and Hojker, S. (2000). Pflugers Arch. 440(5 Suppl), R94-R95.PubMedGoogle Scholar
  41. 41.
    Phenekos, C., Vryonidou, A., Gritzapis, A. D., Baxevanis, C. N., Goula, M., and Papamichail, M. (2004). Neuroimmunomodulation 11, 209–213.PubMedCrossRefGoogle Scholar
  42. 42.
    McLachlan, S. M., Taverne, J., Atherton, M. C., et al., (1990). Clin. Exp. Immunol. 79, 175–181.PubMedCrossRefGoogle Scholar
  43. 43.
    Kocjan, T., Wraber, B., Kocijancic, A., and Hojker, S. (2004). J. Endocrinol. Invest. 27, 302–307.PubMedGoogle Scholar
  44. 44.
    Taniguchi, Y., Kohno, K., Inoue, S. I., et al. (2003). Int. Immunopharmacol. 3, 1313–1324.PubMedCrossRefGoogle Scholar
  45. 45.
    Ajjan, R. A., Watson, P. F., and Weetman, A. P. (1996). Adv. Neuroimmunol. 6, 359–386.PubMedCrossRefGoogle Scholar
  46. 46.
    Pang, X. P., Hershnan, J. M., Chang, M., and Eugene, A. (1989). Endocrinology 125, 1783–1788.PubMedGoogle Scholar
  47. 47.
    Diez, J. J., Hernanz, A., Medina, S., Bayon, C., and Iglesias, P. (2002). Clin. Endocrinol. 57, 515–521.CrossRefGoogle Scholar
  48. 48.
    Çelik, I., Akalin, S., and Erbas, T. (1995). Eur. J. Endocrinol. 132, 668–672.PubMedGoogle Scholar
  49. 49.
    Senturk, T., Kocaci, L. D., Kok, F., Kadikoylu, G., and Bolaman, Z. (2003). Clin. Invest. Med. 26, 58–63.PubMedGoogle Scholar
  50. 50.
    Chopra, I. J., Sakane, S., and Chuo Teco, G. N. (1991). J. Clin. Endocrinol. Metab. 72, 1113–1116.PubMedCrossRefGoogle Scholar
  51. 51.
    Hidaka, Y., Okumura, M., Fukata, S., et al. (1999). Thyroid 9, 149–153.PubMedGoogle Scholar
  52. 52.
    Miyauchi, S., Matsuura, B., and Onji, M. (2000). Thyroid 10, 815–819.PubMedCrossRefGoogle Scholar
  53. 53.
    Tamaru, M., Matsuura, B., and Onji, M. (1999). Eur. J. Endocrinol. 141, 111–116.PubMedCrossRefGoogle Scholar
  54. 54.
    Mysliwiec, J., Kretowski, A., Topolska, J., et al. (2001). Horm. Metab. Res. 33, 739–743.PubMedCrossRefGoogle Scholar
  55. 55.
    Bossowski, A., and Urban, M. (2001). J. Pediatr. Endocrinol. Metab. 14, 741–747.PubMedGoogle Scholar
  56. 56.
    Mysliwiec, J., Kretowski, A., Szelachowska, M., Mikita, A., and Kinalska, I. (1999). Rocz. Akad. Med. Bialymst. 44, 160–169.PubMedGoogle Scholar
  57. 57.
    Mysliwiec, J., Kretowski, A., Stepien, A., Mironczuk, K., and Kinalska, I. (2003). Int. Immunopharmacol. 3, 549–552.PubMedCrossRefGoogle Scholar
  58. 58.
    Takeoka, K., Watanabe, M., Matsuzuko, F., Miyauchi, A., and Iwatani, Y. (2004). Thyroid. 14, 201–205.PubMedCrossRefGoogle Scholar
  59. 59.
    Akamizu, T. (2003). Autoimmunity 36, 361–366.PubMedCrossRefGoogle Scholar
  60. 60.
    Komiya, I., Yamada, T., Sato, A., Kouki, T., Nishimori, T., and Takasu, N. (2001). J. Clin. Endocrinol. Metab. 86, 3540–3544.PubMedCrossRefGoogle Scholar
  61. 61.
    Wiktorska, J., Lewinski, A., and Sewerynem, E. (2002). Endokrynologia Polska 53, 357–363.Google Scholar
  62. 62.
    Wilson, R., McKillop, J. H., Pearson, C., Burnett, A. K., and Thomson, J. A. (1988). Clin. Exp. Immunol 73, 312–315.PubMedGoogle Scholar
  63. 63.
    Michelangeli, V., Poon, C., Taft, J., Newnham, H., Topliss, D., and Colman, P. (1998). Thyroid 8, 119–124.PubMedCrossRefGoogle Scholar
  64. 64.
    McLachlan, S. M., Taverne, J., Atherton, M. C., et al. (1990). Clin. Exp. Immunol. 79, 175–181.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc 2006

Authors and Affiliations

  • Cihangir Erem
    • 1
  • Orhan Deger
    • 2
  • Ercüment Ovali
    • 3
  • Yasam Barlak
    • 2
  1. 1.Department of Internal Medicine Division of Endocrinology and MetabolismKaradeniz Technical University Faculty of MedicineTrabzonTurkey
  2. 2.Department of BiochemistryKaradeniz Technical University Faculty of MedicineTrabzonTurkey
  3. 3.Division of HematologyKaradeniz Technical University Faculty of MedicineTrabzonTurkey

Personalised recommendations