Endocrine

, Volume 27, Issue 2, pp 189–200

A review of the multiple actions of melatonin on the immune system

  • Antonio Carrillo-Vico
  • Juan M. Guerrero
  • Patricia J. Lardone
  • Russel J. Reiter
Article

Abstract

This review summarizes the numerous observations published in recent years which have shown that one of the most significant of melatonin’s pleiotropic effects is the regulation of the immune system. The overview summarizes the immune effects of pinealectomy and the association between rhythmic melatonin production and adjustments in the immune system as markers of melatonin’s immunomodulatory actions. The effects of both in vivo and in vitro melatonin administration on non-specific, humoral, and cellular immune responses as well as on cellular proliferation and immune mediator production are presented. One of the main features that distinguishes melatonin from the classical hormones is its synthesis by a number of nonendocrine extrapineal organs, including the immune system. Herein, we summarize the presence of immune system-synthesized melatonin, its direct immunomodulatory effects on cytokine production, and its masking effects on exogenous melatonin action. The mechanisms of action of melatonin in the immune system are also discussed, focusing attention on the presence of membrane and nuclear receptors and the characterization of several physiological roles mediated by some receptor analogs in immune cells. The review focuses on melatonin’s actions in several immune pathologies including infection, inflammation, and autoimmunity together with the relation between melatonin, immunity, and cancer.

Key Words

Melatonin immune system pineal gland neuroimmunomodulation extrapineal melatonin melatonin receptors immune pathologies 

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References

  1. 1.
    Lerner, A. B., Case, J. D., Takahashi, Y., Lee, T. H., and Mori, W. (1958). J. Am. Chem. Soc. 80, 2587–2589.Google Scholar
  2. 2.
    Axelrod, J. and Weissbach, H. (1960). Science 131, 1312.PubMedGoogle Scholar
  3. 3.
    Lovenberg, W., Weissbach, H., and Udenfriend, S. (1962). J. Biol. Chem. 237, 89–93.PubMedGoogle Scholar
  4. 4.
    Lovenberg, W., Jequier, E., and Sjoerdsma, A. (1967). Science 155, 217–219.PubMedGoogle Scholar
  5. 5.
    Arendt, J. and Skene, D. J. (2005). Sleep Med. Rev. 9, 25–39.PubMedGoogle Scholar
  6. 6.
    Rajaratnam, S. M. and Arendt, J. (2001). Lancet 358, 999–1005.PubMedGoogle Scholar
  7. 7.
    Reiter, R. J. (2003). Best Pract. Res. Clin. Endocrinol. Metab. 17, 273–285.PubMedGoogle Scholar
  8. 8.
    Macchi, M. M. and Bruce, J. N. (2004). Front. Neuroendocrinol. 25, 177–195.PubMedGoogle Scholar
  9. 9.
    Hardeland, R. and Poeggeler, B. (2003). J. Pineal Res. 34, 233–241.PubMedGoogle Scholar
  10. 10.
    Kvetnoy, I. (2002). Neuro. Endocrinol. Lett. 23(Suppl. 1), 92–96.PubMedGoogle Scholar
  11. 11.
    Kvetnoy, I. M. (1999). Histochem. J. 31, 1–12.PubMedGoogle Scholar
  12. 12.
    carrillo-Vico, A., Calvo, J. R., Abreu, P., et al. (2004). FASEB J. 18, 537–539.PubMedGoogle Scholar
  13. 13.
    Cardinali, D. P., Golombek, D. A., Rosenstein, R. E., Cutrera, R. A., and Esquifino, A. I. (1997). J. Pineal Res. 23, 32–39.PubMedGoogle Scholar
  14. 14.
    Blalock, J. E. (2005). J. Intern. Med. 257, 126–138.PubMedGoogle Scholar
  15. 15.
    Vaughan, M. K. and Reiter, R. J. (1971). Tex. Rep. Biol. Med. 29, 579–586.PubMedGoogle Scholar
  16. 16.
    McKinney, T. D., Vaughan, M. K., and Reiter, R. J. (1975). Physiol. Behav. 15, 213–216.PubMedGoogle Scholar
  17. 17.
    Cunnane, S. C., Horrobin, D. F., Manku, M. S., and Oka, M. (1979). Endocr. Res. Commun. 6, 311–319.PubMedGoogle Scholar
  18. 18.
    Brainard, G. C., Watson-Whitmeyer, M., Knobler, R. L., and Lublin, F. D. (1988). Ann. NY Acad. Sci. 540, 704–706.PubMedGoogle Scholar
  19. 19.
    Maestroni, G. J., Conti, A., and Pierpaoli, W. (1986). J. Neuroimmunol. 13, 19–30.PubMedGoogle Scholar
  20. 20.
    Csaba, G. and Barath, P. (1975). Endocrinol. Exp. 9, 59–67.PubMedGoogle Scholar
  21. 21.
    Fraschini, F., Ferioli, M. E., Nebuloni, R., and Scalabrino, G. (1980). J. Neural Transm. 48, 209–221.PubMedGoogle Scholar
  22. 22.
    Scalabrino, G., Ferioli, M. E., Basagni, M., Nebuloni, R., and Fraschini, F. (1979). Am. J. Physiol. 237, E6–10.PubMedGoogle Scholar
  23. 23.
    Scalabrino, G., Ferioli, M. E., Nebuloni, R., and Fraschini, F. (1979). Endocrinology 104, 377–384.PubMedGoogle Scholar
  24. 24.
    Jankovic, B. D., Knezevic, Z., Kojic, L., and Nikolic, V. (1994). Ann. NY Acad. Sci. 719, 398–409.PubMedGoogle Scholar
  25. 25.
    Jankovic, B. D., Isakovic, K., and Petrovic, S. (1970). Immunology 18, 1–6.PubMedGoogle Scholar
  26. 26.
    Beskonakli, E., Palaoglu, S., Aksaray, S., Alanoglu, G., Turhan, T., and Taskin, Y. (2001). Neurosurg. Rev. 24, 26–30.PubMedGoogle Scholar
  27. 27.
    Beskonakli, E., Palaoglu, S., Renda, N., Kulacoglu, S., Turhan, T., and Taskin, Y. (2000). J. Clin. Neurosci. 7, 320–324.PubMedGoogle Scholar
  28. 28.
    Molinero, P., Soutto, M., Benot, S., Hmadcha, A., and Guerrero, J. M. (2000). J. Neuroimmunol. 103, 180–188.PubMedGoogle Scholar
  29. 29.
    Liebmann, P. M., Hofer, D., Felsner, P., Wolfler, A., and Schauenstein, K. (1996). J. Neuroimmunol. 67, 137–142.PubMedGoogle Scholar
  30. 30.
    Vermeulen, M., Palermo, M., and Giordano, M. (1993). J. Neuroimmunol. 43, 97–101.PubMedGoogle Scholar
  31. 31.
    Mocchegiani, E., Bulian, D., Santarelli, L., et al. (1996). J. Pharmacol. Exp. Ther. 277, 1200–1208.PubMedGoogle Scholar
  32. 32.
    del Gobbo, V., Libri, V., Villani, N., Calio, R., and Nistico, G. (1989). Int. J. Immunopharmacol. 11, 567–573.PubMedGoogle Scholar
  33. 33.
    Libri, V., Del, G. V., Villani, N., Calio, R., and Nistico, G. (1990). Pharmacol. Res. 22(Suppl. 3), 52.PubMedGoogle Scholar
  34. 34.
    Yellon, S. M., Teasley, L. A., Fagoaga, O. R., Nguyen, H. C., Truong, H. N., and Nehlsen-Cannarella, L. (1999). J. Pineal Res. 27, 243–248.PubMedGoogle Scholar
  35. 35.
    Haldar, C. and Singh, R. (2001). J. Exp. Zool. 289, 90–98.PubMedGoogle Scholar
  36. 36.
    Jankovic, B. D., Knezevic, Z., Kojic, L., and Nikolic, V. (1994). Ann. NY Acad. Sci. 719, 398–409.PubMedGoogle Scholar
  37. 37.
    Rosolowska-Huszcz, D., Thaela, M. J., Jagura, M., Stepien, D., and Skwarlo-Sonta, K. (1991). J. Pineal Res. 10, 190–195.PubMedGoogle Scholar
  38. 38.
    Rodriguez, A. B. and Lea, R. W. (1994). J. Pineal Res. 16, 159–166.PubMedGoogle Scholar
  39. 39.
    Maxwell, M. H. (1981). Res. Vet. Sci. 31, 113–115.PubMedGoogle Scholar
  40. 40.
    Moore, C. B., Siopes, T. D., Steele, C. T., and Underwood, H. (2002). Gen. Comp Endocrinol. 126, 352–358.PubMedGoogle Scholar
  41. 41.
    Minton, J. E., Reddy, P. G., and Blecha, F. (1991). J. Anim. Sci. 69, 565–570.PubMedGoogle Scholar
  42. 42.
    Haus, E., Lakatua, D. J., Swoyer, J., and Sackett-Lundeen, L. (1983). Am. J. Anat. 168, 467–517.PubMedGoogle Scholar
  43. 43.
    Paglieroni, T. G. and Holland, P. V. (1994). Transfusion 34, 512–516.PubMedGoogle Scholar
  44. 44.
    Fernandes, G., Carandente, F., Halberg, E., Halberg, F., and Good, R. A. (1979). J. Immunol. 123, 622–625.PubMedGoogle Scholar
  45. 45.
    Petrovsky, N. and Harrison, L. C. (1997). J. Immunol. 158, 5163–5168.PubMedGoogle Scholar
  46. 46.
    Vaughan, M. K., Vaughan, G. M., and Reiter, R. J. (1973). J. Reprod. Fertil. 32, 9–14.PubMedGoogle Scholar
  47. 47.
    Vriend, J. and Lauber, J. K. (1973). Nature 244, 37–38.PubMedGoogle Scholar
  48. 48.
    Brainard, G. C., Knobler, R. L., Podolin, P. L., Lavasa, M., and Lublin, F. D. (1987). Life Sci. 40, 1319–1326.PubMedGoogle Scholar
  49. 49.
    Nelson, R. J. (2004). Trends Immunol. 25, 187–192.PubMedGoogle Scholar
  50. 50.
    Kuci, S., Becker, J., Veit, G., et al. (1988). Neuro. Endocrinol. Lett. 10, 65–79.Google Scholar
  51. 51.
    Haldar, C., Haussler, D., and Gupta, D. (1992). J. Pineal Res. 12, 79–83.PubMedGoogle Scholar
  52. 52.
    Demas, G. E., Klein, S. L., and Nelson, R. J. (1996). J. Comp. Physiol. [A] 179, 819–825.Google Scholar
  53. 53.
    Haldar, C., Singh, R., and Guchhait, P. (2001). Chronobiol. Int. 18, 61–69.PubMedGoogle Scholar
  54. 54.
    Giordano, M., Vermeulen, M., and Palermo, M. S. (1993). FASEB J. 7, 1052–1054.PubMedGoogle Scholar
  55. 55.
    Prendergast, B. J., Hotchkiss, A. K., and Nelson, R. J. (2003). J. Biol. Rhythms 18, 473–480.PubMedGoogle Scholar
  56. 56.
    Cardinali, D. P. and Esquifino, A. I. (2003). Neurosignals 12, 267–282.PubMedGoogle Scholar
  57. 57.
    Rodriguez, A. B., Marchena, J. M., Nogales, G., Duran, J., and Barriga, C. (1999). J. Pineal Res. 26, 35–42.PubMedGoogle Scholar
  58. 58.
    Terron, M. P., Paredes, S. D., Barriga, C., Ortega, E., and Rodriguez, A. B. (2004). J. Comp. Physiol. [B] 174, 421–427.Google Scholar
  59. 59.
    Nelson, R. J. and Drazen, D. L. (1999). Reprod. Nutr. Dev. 39, 383–398.PubMedGoogle Scholar
  60. 60.
    Vaughan, M. K., Vaughan, G. M., Reiter, R. J., and Blask, D. E. (1976). Experientia 32, 1341–1342.PubMedGoogle Scholar
  61. 61.
    Vaughan, M. K., Hubbard, G. B., Champney, T. H., Vaughan, G. M., Little, J. C., and Reiter, R. J. (1987). Am. J. Anat. 179, 131–136.PubMedGoogle Scholar
  62. 62.
    Rai, S. and Haldar, C. (2003). Comp. Biochem. Physiol. C. Toxicol. Pharmacol. 136, 319–328.PubMedGoogle Scholar
  63. 63.
    Tian, Y. M., Zhang, G. Y., and Dai, Y. R. (2003). Immunol. Lett. 88, 101–104.PubMedGoogle Scholar
  64. 64.
    Haldar, C., Rai, S., and Singh, R. (2004). Steroids 69, 367–377.PubMedGoogle Scholar
  65. 65.
    Aoyama, H., Mori, N., and Mori, W. (1987). Acta Pathol. Jpn. 37, 1143–1148.PubMedGoogle Scholar
  66. 66.
    Mori, W., Aoyama, H., and Mori, N. (1984). Jpn. J. Exp. Med. 54, 255–261.PubMedGoogle Scholar
  67. 67.
    Sze, S. F., Liu, W. K., and Ng, T. B. (1993). J. Neural Transm. Gen. Sect. 94, 115–126.PubMedGoogle Scholar
  68. 68.
    Demas, G. E. and Nelson, R. J. (1998). J. Biol. Rhythms 13, 245–252.PubMedGoogle Scholar
  69. 69.
    Martins, E. Jr., Fernandes, L. C., Bartol, I., Cipolla-Neto, J., and Costa Rosa, L. F. (1998). J. Neuroimmunol. 82, 81–89.PubMedGoogle Scholar
  70. 70.
    Currier, N. L., Sun, L. Z., and Miller, S. C. (2000). J. Neuroimmunol. 104, 101–108.PubMedGoogle Scholar
  71. 71.
    Giordano, M. and Palermo, M. S. (1991). J. Pineal Res. 10, 117–121.PubMedGoogle Scholar
  72. 72.
    Lissoni, P., Marelli, O., Mauri, R., et al. (1986). Chronobiologia 13, 339–343.PubMedGoogle Scholar
  73. 73.
    Belokrylov, G. A., Morozov, V. G., Khavinson, V. K., and Sofronov, B. N. (1976). Biull. Eksp. Biol. Med. 81, 202–204.PubMedGoogle Scholar
  74. 74.
    Anisimov, V. N., Khavinson, V. K., and Morozov, V. G. (1982). Mech. Ageing Dev. 19, 245–258.PubMedGoogle Scholar
  75. 75.
    Champney, T. H., Allen, G. C., Zannelli, M., and Beausang, L. A. (1998). J. Pineal Res. 25, 142–146.PubMedGoogle Scholar
  76. 76.
    Moore, C. B. and Siopes, T. D. (2002). Gen. Comp. Endocrinol. 129, 122–126.PubMedGoogle Scholar
  77. 77.
    Pioli, C., Caroleo, M. C., Nistico, G., and Doria, G. (1993). Int. J. Immunopharmacol. 15, 463–468.PubMedGoogle Scholar
  78. 78.
    Liu, F., Ng, T. B., and Fung, M. C. (2001). J. Neural Transm. 108, 397–405.PubMedGoogle Scholar
  79. 79.
    Raghavendra, V., Singh, V., Kulkarni, S. K., and Agrewala, J. N. (2001). Mol. Cell Biochem. 221, 57–62.PubMedGoogle Scholar
  80. 80.
    Sainz, R. M., Mayo, J. C., Uria, H., et al. (1995). J. Pineal Res. 19, 178–188.PubMedGoogle Scholar
  81. 81.
    Yu, Q., Miller, S. C., and Osmond, D. G. (2000). J. Pineal Res. 29, 86–93.PubMedGoogle Scholar
  82. 82.
    Maestroni, G. J., Conti, A., and Pierpaoli, W. (1986). J. Neuroimmunol. 13, 19–30.PubMedGoogle Scholar
  83. 83.
    Pierpaoli, W. and Maestroni, G. J. (1987). Immunol. Lett. 16, 355–361.PubMedGoogle Scholar
  84. 84.
    Caroleo, M. C., Frasca, D., Mancini, C., Nistico, G., and Doria, G. (1990). Pharmacol. Res. 22(Suppl. 3), 53.PubMedGoogle Scholar
  85. 85.
    Caroleo, M. C., Nistico, G., and Doria, G. (1992). Pharmacol. Res. 26(Suppl. 2), 34–37.PubMedGoogle Scholar
  86. 86.
    Caroleo, M. C., Frasca, D., Nistico, G., and Doria, G. (1992). Immunopharmacology 23, 81–89.PubMedGoogle Scholar
  87. 87.
    Maestroni, G. J., Conti, A., and Pierpaoli, W. (1987). Clin. Exp. Immunol. 68, 384–391.PubMedGoogle Scholar
  88. 88.
    Maestroni, G. J., Conti, A., and Pierpaoli, W. (1988). Immunology 63, 465–469.PubMedGoogle Scholar
  89. 89.
    Maestroni, G. J. and Conti, A. (1989). Int. J. Immunopharmacol. 11, 333–340.PubMedGoogle Scholar
  90. 90.
    Maestroni, G. J., Conti, A., and Pierpaoli, W. (1987). Clin. Exp. Immunol. 68, 384–391.PubMedGoogle Scholar
  91. 91.
    Wajs, E., Kutoh, E., and Gupta, D. (1995). Eur. J. Endocrinol. 133, 754–760.PubMedGoogle Scholar
  92. 92.
    Moore, C. B. and Siopes, T. D. (2003). Gen. Comp. Endocrinol. 131, 258–263.PubMedGoogle Scholar
  93. 93.
    Majewski, P., Dziwinski, T., Pawlak, J., Waloch, M., and Skwarlo-Sonta, K. (2005). Life Sci. 76, 1907–1920.PubMedGoogle Scholar
  94. 94.
    Provinciali, M., Di Stefano, G., Bulian, D., Stronati, S., and Fabris, N. (1997). Life Sci. 61, 857–864.PubMedGoogle Scholar
  95. 95.
    Pahlavani, M. A., Vargas, D. A., Evans, T. R., Shu, J. H., and Nelson, J. F. (2002). Exp. Biol. Med. (Maywood.) 227, 201–207.Google Scholar
  96. 96.
    Bernard, S., Macedo, N., Malpaux, B., and Chemineau, P. (2001). J. Pineal Res. 31, 248–255.PubMedGoogle Scholar
  97. 97.
    Fraschini, F., Scaglione, F., Franco, P., Demartini, G., Lucini, V., and Stankov, B. (1990). Acta Oncol. 29, 775–776.PubMedGoogle Scholar
  98. 98.
    Drazen, D. L., Klein, S. L., Yellon, S. M., and Nelson, R. J. (2000). J. Pineal Res. 28, 34–40.PubMedGoogle Scholar
  99. 99.
    Kriegsfeld, L. J., Drazen, D. L., and Nelson, R. J. (2001). J. Pineal Res. 30, 193–198.PubMedGoogle Scholar
  100. 100.
    Lopez-Gonzalez, M. A., Guerrero, J. M., Sanchez, B., and Delgado, F. (1998). Neurosci. Lett. 247, 131–134.PubMedGoogle Scholar
  101. 101.
    Kuhlwein, E. and Irwin, M. (2001). J. Neuroimmunol. 117, 51–57.PubMedGoogle Scholar
  102. 102.
    Wolfler, A., Schauenstein, K., and Liebmann, P. M. (1998). Life Sci. 63, 835–842.PubMedGoogle Scholar
  103. 103.
    Pahlavani, M. A. and Harris, M. D. (1997). Immunopharmacol. Immunotoxicol. 19, 327–337.PubMedGoogle Scholar
  104. 104.
    Pawlikowski, M., Lyson, K., Kunert-Radek, J., and Stepien, H. (1988). J. Neural. Transm. 73, 161–166.PubMedGoogle Scholar
  105. 105.
    Lewinski, A., Zelazowski, P., Sewerynek, E., Zerek-Melen, G., Szkudlinski, M., and Zelazowska, E. (1989). J. Pineal Res. 7, 153–164.PubMedGoogle Scholar
  106. 106.
    Di Stefano, A. and Paulesu, L. (1994). J. Pineal Res. 17, 164–169.PubMedGoogle Scholar
  107. 107.
    Capelli, E., Campo, I., Panelli, S., et al. (2002). Int. Immunopharmacol. 2, 885–892.PubMedGoogle Scholar
  108. 108.
    Colombo, L. L., Chen, G. J., Lopez, M. C., and Watson, R. R. (1992). Immunol. Lett. 33, 123–126.PubMedGoogle Scholar
  109. 109.
    García-Mauriño, S., Gonzalez-Haba, M. G., Calvo, J. R., et al. (1997). J. Immunol. 159, 574–581.PubMedGoogle Scholar
  110. 110.
    García-Mauriño, S., Pozo, D., Calvo, J. R., and Guerrero, J. M. (2000). J. Pineal Res. 29, 129–137.PubMedGoogle Scholar
  111. 111.
    Steinhilber, D., Brungs, M., Werz, O., et al. (1995). J. Biol. Chem. 270, 7037–7040.PubMedGoogle Scholar
  112. 112.
    Morrey, K. M., McLachlan, J. A., Serkin, C. D., and Bakouche, O. (1994). J. Immunol. 153, 2671–2680.PubMedGoogle Scholar
  113. 113.
    García-Mauriño, S., Pozo, D., Carrillo-Vico, A., Calvo, J. R., and Guerrero, J. M. (1999). Life Sci. 65, 2143–2150.PubMedGoogle Scholar
  114. 114.
    Fjaerli, O., Lund, T., and Osterud, B. (1999). J. Pineal Res. 26, 50–55.PubMedGoogle Scholar
  115. 115.
    Rapaport, S. I. and Rao, L. V. (1992). Arterioscler. Thromb. 12, 1111–1121.PubMedGoogle Scholar
  116. 116.
    Gilad, E., Wong, H. R., Zingarelli, B., et al. (1998). FASEB J. 12, 685–693.PubMedGoogle Scholar
  117. 117.
    Zhang, S., Li, W., Gao, Q., and Wei, T. (2004). Eur. J. Pharmacol. 501, 25–30.PubMedGoogle Scholar
  118. 118.
    Maestroni, G. J., Covacci, V., and Conti, A. (1994). Cancer Res. 54, 2429–2432.PubMedGoogle Scholar
  119. 119.
    Maestroni, G. J., Hertens, E., Galli, P., Conti, A., and Pedrinis, E. (1996). J. Pineal Res. 21, 131–139.PubMedGoogle Scholar
  120. 120.
    Maestroni, G. J., Zammaretti, F., and Pedrinis, E. (1999). J. Pineal Res. 27, 145–153.PubMedGoogle Scholar
  121. 121.
    Pieri, C., Recchioni, R., Moroni, F., et al. (1998). J. Pineal Res. 24, 43–49.PubMedGoogle Scholar
  122. 122.
    Silva, S. O., Rodrigues, M. R., Carvalho, S. R., Catalani, L. H., Campa, A., and Ximenes, V. F. (2004). J. Pineal Res. 37, 171–175.PubMedGoogle Scholar
  123. 123.
    Silva, S. O., Rodrigues, M. R., Ximenes, V. F., Bueno-da-Silva, A. E., Amarante-Mendes, G. P., and Campa, A. (2004). J. Neuroimmunol. 156, 146–152.PubMedGoogle Scholar
  124. 124.
    Rodriguez, A. B., Nogales, G., Ortega, E., and Barriga, C. (1998). J. Pineal Res. 24, 9–14.PubMedGoogle Scholar
  125. 125.
    Rodriguez, A. B., Terron, M. P., Duran, J., Ortega, E., and Barriga, C. (2001). J. Pineal Res. 31, 31–38.PubMedGoogle Scholar
  126. 126.
    Rodriguez, A. B., Ortega, E., Lea, R. W., and Barriga, C. (1997). Mol. Cell Biochem. 168, 185–190.PubMedGoogle Scholar
  127. 127.
    Tan, D. X., Manchester, L. C., Hardeland, R., et al. (2003). J. Pineal Res. 34, 75–78.PubMedGoogle Scholar
  128. 128.
    Gern, W. A. and Ralph, C. L. (1979). Science 204, 183–184.PubMedGoogle Scholar
  129. 129.
    Bubenik, G. A., Brown, G. M., and Grota, L. G. (1976). Brain Res. 118, 417–427.PubMedGoogle Scholar
  130. 130.
    Raikhlin, N. T., Kvetnoy, I. M., and Tolkachev, V. N. (1975). Nature 255, 344–345.PubMedGoogle Scholar
  131. 131.
    Bubenik, G. A. (2002). Dig. Dis. Sci. 47, 2336–2348.PubMedGoogle Scholar
  132. 132.
    Slominski, A., Wortsman, J., and Tobin, D. J. (2005). FASEB J. 19, 176–194.PubMedGoogle Scholar
  133. 133.
    Stefulj, J., Hortner, M., Ghosh, M., et al. (2001). J. Pineal Res. 30, 243–247.PubMedGoogle Scholar
  134. 134.
    Conti, A., Conconi, S., Hertens, E., Skwarlo-Sonta, K., Markowska, M., and Maestroni, J. M. (2000). J. Pineal Res. 28, 193–202.PubMedGoogle Scholar
  135. 135.
    Finocchiaro, L. M. and Glikin, G. C. (1998). J. Pineal Res. 24, 22–34.PubMedGoogle Scholar
  136. 136.
    Finocchiaro, L. M., Arzt, E. S., Fernandez-Castelo, S., Criscuolo, M., Finkielman, S., and Nahmod, V. E. (1988). J. Interferon Res. 8, 705–716.PubMedGoogle Scholar
  137. 137.
    Finocchiaro, L. M., Nahmod, V. E., and Launay, J. M. (1991). Biochem. J. 280(Pt. 3), 727–731.PubMedGoogle Scholar
  138. 138.
    Conti, A., Conconi, S., Hertens, E., Skwarlo-Sonta, K., Markowska, M., and Maestroni, J. M. (2000). J. Pineal Res. 28, 193–202.PubMedGoogle Scholar
  139. 139.
    Tan, D. X., Manchester, L. C., Reiter, R. J., et al. (1999). Biochim. Biophys. Acta 1472, 206–214.PubMedGoogle Scholar
  140. 140.
    Carrillo-Vico, A., Lardone, P. J., Fernandez-Santos, J. M., et al. (2005). J. Clin. Endocrinol. Metab. 90, 992–1000.PubMedGoogle Scholar
  141. 141.
    Martins, E. Jr., Ferreira, A. C., Skorupa, A. L., Afeche, S. C., Cipolla-Neto, J., and Costa Rosa, L. F. (2004). J. Leukoc. Biol. 75, 1116–1121.PubMedGoogle Scholar
  142. 142.
    Guerrero, J. M. and Reiter, R. J. (2002). Curr. Top. Med. Chem. 2, 167–179.PubMedGoogle Scholar
  143. 143.
    Maestroni, G. J. (1999). Adv. Exp. Med. Biol. 467, 217–226.PubMedGoogle Scholar
  144. 144.
    Dubocovich, M. L. (1995). Trends Pharmacol. Sci. 16, 50–56.PubMedGoogle Scholar
  145. 145.
    Reppert, S. M., Weaver, D. R., and Ebisawa, T. (1994). Neuron 13, 1177–1185.PubMedGoogle Scholar
  146. 146.
    Reppert, S. M., Godson, C., Mahle, C. D., Weaver, D. R., Slaugenhaupt, S. A., and Gusella, J. F. (1995). Proc. Natl. Acad. Sci. USA 92, 8734–8738.PubMedGoogle Scholar
  147. 147.
    Reppert, S. M., Weaver, D. R., Cassone, V. M., Godson, C., and Kolakowski, L. F. Jr. (1995). Neuron 15, 1003–1015.PubMedGoogle Scholar
  148. 148.
    Dubocovich, M. L., Masana, M. I., and Benloucif, S. (1999). Adv. Exp. Med. Biol. 460, 181–190.PubMedGoogle Scholar
  149. 149.
    Nosjean, O., Ferro, M., Coge, F., et al. (2000). J. Biol. Chem. 275, 31311–31317.PubMedGoogle Scholar
  150. 150.
    Smirnov, A. N. (2001). Biochemistry (Mosc.) 66, 19–26.Google Scholar
  151. 151.
    Liu, Z. M. and Pang, S. F. (1993). J. Endocrinol. 138, 51–57.PubMedGoogle Scholar
  152. 152.
    Yu, Z. H., Yuan, H., Lu, Y., and Pang, S. F. (1991). Neurosci. Lett. 125, 175–178.PubMedGoogle Scholar
  153. 153.
    Pang, C. S. and Pang, S. F. (1992). J. Pineal Res. 12, 167–173.PubMedGoogle Scholar
  154. 154.
    Poon, A. M., Wang, X. L., and Pang, S. F. (1993). J. Pineal Res. 14, 169–177.PubMedGoogle Scholar
  155. 155.
    Wang, X. L., Yuan, H., and Pang, S. F. (1993). Zhongguo. Yao. Li. Xue. Bao. 14, 292–295.PubMedGoogle Scholar
  156. 156.
    Poon, A. M. and Pang, S. F. (1992). Life Sci. 50, 1719–1726.PubMedGoogle Scholar
  157. 157.
    Poon, A. M. and Pang, S. F. (1994). Life Sci. 54, 1441–1448.PubMedGoogle Scholar
  158. 158.
    Rafii-El-Idrissi, M., Calvo, J. R., Pozo, D., Harmouch, A., and Guerrero, J. M. (1995). J. Neuroimmunol. 57, 171–178.PubMedGoogle Scholar
  159. 159.
    Rafii-El-Idrissi, M., Calvo, J. R., Giordano, M., and Guerrero, J. M. (1996). J. Pineal Res. 20, 33–38.PubMedGoogle Scholar
  160. 160.
    Liu, Z. M. and Pang, S. F. (1992). Biol. Signals. 1, 250–256.PubMedGoogle Scholar
  161. 161.
    Poon, A. M., Liu, Z. M., Tang, F., and Pang, S. F. (1994). Eur. J. Endocrinol. 130, 320–324.PubMedGoogle Scholar
  162. 162.
    Lopez-Gonzalez, M. A., Martin-Cacao, A., Calvo, J. R., Reiter, R. J., Osuna, C., and Guerrero, J. M. (1993). J. Neuroimmunol. 45, 121–126.PubMedGoogle Scholar
  163. 163.
    Martin-Cacao, A., Lopez-Gonzalez, M. A., Reiter, R. J., Calvo, J. R., and Guerrero, J. M. (1993). Immunol. Lett. 36, 59–63.PubMedGoogle Scholar
  164. 164.
    Lopez-Gonzalez, M. A., Calvo, J. R., Osuna, C., Rubio, A., and Guerrero, J. M. (1992). J. Pineal Res. 12, 174–180.PubMedGoogle Scholar
  165. 165.
    Lopez-Gonzalez, M. A., Calvo, J. R., Osuna, C., and Guerrero, J. M. (1992). J. Pineal Res. 12, 97–104.PubMedGoogle Scholar
  166. 166.
    Lopez-Gonzalez, M. A., Calvo, J. R., Osuna, C., Rubio, A., and Guerrero, J. M. (1992). Neurosci. Lett. 136, 150–152.PubMedGoogle Scholar
  167. 167.
    Barjavel, M. J., Mamdouh, Z., Raghbate, N., and Bakouche, O. (1998). J. Immunol. 160, 1191–1197.PubMedGoogle Scholar
  168. 168.
    Garcia-Perganeda, A., Guerrero, J. M., Rafii-El-Idrissi, M., Paz Romero, M., Pozo, D., and Calvo, J. R. (1999). J. Neuroimmunol. 95, 85–94.PubMedGoogle Scholar
  169. 169.
    Garcia-Perganeda, A., Pozo, D., Guerrero, J. M., and Calvo, J. R. (1997). J. Immunol. 159, 3774–3781.PubMedGoogle Scholar
  170. 170.
    Liu, Z., Zhao, Y., and Peng, S. (1995). Sci. China B 38, 1455–1461.PubMedGoogle Scholar
  171. 171.
    Rafii-El-Idrissi, M., Calvo, J. R., Harmouch, A., Garcia-Maurino, S., and Guerrero, J. M. (1998). J. Neuroimmunol. 86, 190–197.PubMedGoogle Scholar
  172. 172.
    Pozo, D., Delgado, M., Fernandez-Santos, J. M., et al. (1997). FASEB J. 11, 466–473.PubMedGoogle Scholar
  173. 173.
    Carrillo-Vico, A., Garcia-Maurino, S., Calvo, J. R., and Guerrero, J. M. (2003). FASEB J. 17, 755–757.PubMedGoogle Scholar
  174. 174.
    Pozo, D., Garcia-Maurino, S., Guerrero, J. M., and Calvo, J. R. (2004). J. Pineal Res. 37, 48–54.PubMedGoogle Scholar
  175. 175.
    Carrillo-Vico, A., Garcia-Perganeda, A., Naji, L., Calvo, J. R., Romero, M. P., and Guerrero, J. M. (2003). Cell Mol. Life Sci. 60, 2272–2278.PubMedGoogle Scholar
  176. 176.
    Dubocovich, M. L., Rivera-Bermudez, M. A., Gerdin, M. J., and Masana, M. I. (2003). Front. Biosci. 8, d1093-d1108.PubMedGoogle Scholar
  177. 177.
    Missbach, M., Jagher, B., Sigg, I., Nayeri, S., Carlberg, C., and Wiesenberg, I. (1996). J. Biol. Chem. 271, 13515–13522.PubMedGoogle Scholar
  178. 178.
    Drazen, D. L., Bilu, D., Bilbo, S. D., and Nelson, R. J. (2001). Am. J. Physiol Regul. Integr. Comp. Physiol. 280, R1476-R1482.PubMedGoogle Scholar
  179. 179.
    Drazen, D. L. and Nelson, R. J. (2001). Neuroendocrinology 74, 178–184.PubMedGoogle Scholar
  180. 180.
    Markowska, M., Mrozkowiak, A., Pawlak, J., and Skwarlo-Sonta, K. (2004). J. Pineal Res. 37, 207–212.PubMedGoogle Scholar
  181. 181.
    García-Mauriño, S., Gonzalez-Haba, M. G., Calvo, J. R., Goberna, R., and Guerrero, J. M. (1998). J. Neuroimmunol. 92, 76–84.PubMedGoogle Scholar
  182. 182.
    Ben Nathan, D., Maestroni, G. J., Lustig, S., and Conti, A. (1995). Arch. Virol. 140, 223–230.PubMedGoogle Scholar
  183. 183.
    Bonilla, E., Valero-Fuenmayor, N., Pons, H., and Chacin-Bonilla, L. (1997). Cell Mol. Life Sci. 53, 430–434.PubMedGoogle Scholar
  184. 184.
    Bonilla, E., Rodon, C., Valero, N., et al. (2001). Trans. R. Soc. Trop. Med. Hyg. 95, 207–210.PubMedGoogle Scholar
  185. 185.
    Bonilla, E., Valero, N., Chacin-Bonilla, L., et al. (2003). Neurochem. Res. 28, 681–686.PubMedGoogle Scholar
  186. 186.
    Zhang, Z., Araghi-Niknam, M., Liang, B., et al. (1999). Immunology 96, 291–297.PubMedGoogle Scholar
  187. 187.
    d’Emmanuele, d., V, Marzocco, S., Di Paola, R., et al. (2004). J. Pineal Res. 36, 146–154.Google Scholar
  188. 188.
    Gilad, E., Wong, H. R., Zingarelli, B., et al. (1998). FASEB J. 12, 685–693.PubMedGoogle Scholar
  189. 189.
    Reiter, R. J., Calvo, J. R., Karbownik, M., Qi, W., and Tan, D. X. (2000). Ann. NY Acad. Sci. 917, 376–386.PubMedGoogle Scholar
  190. 190.
    Annane, D., Bellissant, E., and Cavaillon, J. M. (2005). Lancet 365, 63–78.PubMedGoogle Scholar
  191. 191.
    Maestroni, G. J. (1996). J. Pineal Res. 20, 84–89.PubMedGoogle Scholar
  192. 192.
    Requintina, P. J. and Oxenkrug, G. F. (2003). Ann. NY Acad. Sci. 993, 325–333.PubMedGoogle Scholar
  193. 193.
    Wu, C. C., Chiao, C. W., Hsiao, G., Chen, A., and Yen, M. H. (2001). J. Pineal Res. 30, 147–156.PubMedGoogle Scholar
  194. 194.
    Sullivan, D. J., Shelby, J., Shao, Y., Affleck, D. G., Hinson, D. M., and Barton, R. G. (1996). J. Surg. Res. 64, 13–18.PubMedGoogle Scholar
  195. 195.
    Crespo, E., Macias, M., Pozo, D., et al. (1999). FASEB J. 13, 1537–1546.PubMedGoogle Scholar
  196. 196.
    Escames, G., Leon, J., Macias, M., Khaldy, H., and Acuna-Castroviejo, D. (2003). FASEB J. 17, 932–934.PubMedGoogle Scholar
  197. 197.
    Sewerynek, E., Melchiorri, D., Chen, L., and Reiter, R. J. (1995). Free Radic. Biol. Med. 19, 903–909.PubMedGoogle Scholar
  198. 198.
    Sewerynek, E., Melchiorri, D., Reiter, R. J., Ortiz, G. G., and Lewinski, A. (1995). Eur. J. Pharmacol. 293, 327–334.PubMedGoogle Scholar
  199. 199.
    Mundigler, G., Delle-Karth, G., Koreny, M., et al. (2002). Crit. Care Med. 30, 536–540.PubMedGoogle Scholar
  200. 200.
    Martins, E. Jr., Ligiro de Oliveira, A. P., Fialho de Araujo, A. M., Tavares, D. L., Cipolla-Neto, J., and Costa Rosa, L. F. (2001). J. Pineal Res. 31, 363–369.PubMedGoogle Scholar
  201. 201.
    Gitto, E., Karbownik, M., Reiter, R. J., et al. (2001). Pediatr. Res. 50, 756–760.PubMedGoogle Scholar
  202. 202.
    Maestroni, G. J., Cardinali, D. P., Esquifino, A. I., and Pandi-Perumal, S. R. (2005). J. Neuroimmunol. 158, 106–111.PubMedGoogle Scholar
  203. 203.
    Cutolo, M., Maestroni, G. J., Otsa, K., et al. (2005). Ann. Rheum. Dis. 64, 212–216.PubMedGoogle Scholar
  204. 204.
    Petrovsky, N. and Harrison, L. C. (1998). Int. Rev. Immunol. 16, 635–649.PubMedGoogle Scholar
  205. 205.
    Cutolo, M., Villaggio, B., Candido, F., et al. (1999). Ann. NY Acad. Sci. 876, 246–254.PubMedGoogle Scholar
  206. 206.
    Maestroni, G. J., Sulli, A., Pizzorni, C., Villaggio, B., and Cutolo, M. (2002). Ann. NY Acad. Sci. 966, 271–275.PubMedGoogle Scholar
  207. 207.
    Chen, Q. and Wei, W. (2002). Int. Immunopharmacol. 2, 1443–1449.PubMedGoogle Scholar
  208. 208.
    Constantinescu, C. S., Hilliard, B., Ventura, E., and Rostami, A. (1997). Pathobiology 65, 190–194.PubMedGoogle Scholar
  209. 209.
    Maestroni, G. J. (2001). Expert. Opin. Investig. Drugs 10, 467–476.PubMedGoogle Scholar
  210. 210.
    Kang, J. C., Ahn, M., Kim, Y. S., et al. (2001). J. Vet. Sci. 2, 85–89.PubMedGoogle Scholar
  211. 211.
    Sandyk, R. (1997). Int. J. Neurosci. 90, 129–133.PubMedGoogle Scholar
  212. 212.
    Lenz, S. P., Izui, S., Benediktsson, H., and Hart, D. A. (1995). Int. J. Immunopharmacol. 17, 581–592.PubMedGoogle Scholar
  213. 213.
    Haga, H. J., Brun, J. G., Rekvig, O. P., and Wetterberg, L. (1999). Lupus 8, 269–273.PubMedGoogle Scholar
  214. 214.
    Lechner, O., Dietrich, H., Oliveira dos, S. A., et al. (2000). J. Autoimmun. 14, 325–333.PubMedGoogle Scholar
  215. 215.
    Calvo, J. R., Guerrero, J. M., Osuna, C., Molinero, P., and Carrillo-Vico, A. (2002). J. Pineal Res. 32, 277–278.PubMedGoogle Scholar
  216. 216.
    Chada, S., Ramesh, R., and Mhashilkar, A. M. (2003). Curr. Opin. Mol. Ther. 5, 463–474.PubMedGoogle Scholar
  217. 217.
    Akazawa, T., Masuda, H., Saeki, Y., et al. (2004). Cancer Res. 64, 757–764.PubMedGoogle Scholar
  218. 218.
    Lissoni, P. (2002). Support Care Cancer 10, 110–116.PubMedGoogle Scholar
  219. 219.
    Lissoni, P., Bolis, S., Brivio, F., and Fumagalli, L. (2000). Anticancer Res. 20, 2103–2105.PubMedGoogle Scholar
  220. 220.
    Lissoni, P. (2000). Ann. NY Acad. Sci. 917, 560–567.PubMedGoogle Scholar
  221. 221.
    Lissoni, P., Pittalis, S., Ardizzoia, A., et al. (1996). Support Care Cancer 4, 313–316.PubMedGoogle Scholar
  222. 222.
    Neri, B., de Leonardis, V., Gemelli, M. T., et al. (1998). Anticancer Res. 18, 1329–1332.PubMedGoogle Scholar
  223. 223.
    Lissoni, P., Barni, S., Tancini, G., et al. (1994). J. Biol. Regul. Homeost. Agents 8, 126–129.PubMedGoogle Scholar
  224. 224.
    Van Gool, S. W., Van Den, H. L., and Ceuppens, J. L. (2000). Med. Pediatr. Oncol. 34, 1–9.PubMedGoogle Scholar
  225. 225.
    Jung, F. J., Yang, L., Harter, L., et al. (2004). J. Pineal Res. 37, 36–41.PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2005

Authors and Affiliations

  • Antonio Carrillo-Vico
    • 1
  • Juan M. Guerrero
    • 1
  • Patricia J. Lardone
    • 1
  • Russel J. Reiter
    • 2
  1. 1.Department of Medical Biochemistry and Molecular BiologyThe University of Seville School of Medicine and Virgen Macarena HospitalSevilleSpain
  2. 2.Department of Cellular and Structural BiologyUniversity of Texas Health Science CenterSan AntonioUSA

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