Modulation by melatonin of the pathogenesis of inflammatory autoimmune diseases

International Journal of Molecular Sciences

Volumn 14, Issue 6, 2013, Pages 11742-11766

  Lin, Gu Jiun ^a   Huang, Shing Hwa ^b   Chen, Shyi Jou ^a,b   Wang, Chih Hung ^a,b   Chang, Deh Ming ^b   Sytwu, Huey Kang ^a  

^a NATIONAL DEFENSE MEDICAL CENTER   (Taiwan)

^b TRI SERVICE GENERAL HOSPITAL   (Taiwan)

Author keywords

Autoimmune disease; Inflammatory bowel disease; Melatonin; Multiple sclerosis; Rheumatoid arthritis; Systemic lupus erythematosus; Type 1 diabetes mellitus

Indexed keywords

CYCLOOXYGENASE 2; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INDUCIBLE NITRIC OXIDE SYNTHASE; INTERLEUKIN 1BETA; INTERLEUKIN 6; MELATONIN; TUMOR NECROSIS FACTOR ALPHA;

ABSENCE OF SIDE EFFECTS; AUTOIMMUNE DIABETES MELLITUS; AUTOINFLAMMATORY DISEASE; CARDIAC GRAFT REJECTION; COLITIS; CYTOKINE PRODUCTION; DIABETES MELLITUS; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG EFFECT; DRUG EFFICACY; DRUG MEGADOSE; DRUG METABOLISM; DRUG SAFETY; DRUG TOLERABILITY; ENTERITIS; HORMONE ACTION; HORMONE SYNTHESIS; HUMAN; IMMUNOMODULATION; IMMUNOPATHOGENESIS; INSULIN DEPENDENT DIABETES MELLITUS; ISCHEMIA; LOW DRUG DOSE; MULTIPLE SCLEROSIS; NEPHRITIS; NONHUMAN; PANCREAS ISLET BETA CELL; PANCREAS ISLET TRANSPLANTATION; REPERFUSION INJURY; REVIEW; RHEUMATOID ARTHRITIS; SYSTEMIC LUPUS ERYTHEMATOSUS; TH1 TH2 BALANCE; ANIMAL; AUTOIMMUNE DISEASES; BIOSYNTHESIS; CLINICAL TRIAL (TOPIC); DISEASE MODEL; INFLAMMATION;

ANIMALIA;

ANIMALS; AUTOIMMUNE DISEASES; CLINICAL TRIALS AS TOPIC; DISEASE MODELS, ANIMAL; HUMANS; INFLAMMATION; MELATONIN;

EID: 84879007548     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms140611742     Document Type: Review

References (156)

1. Tan, D.X.; Manchester, L.C.; Hardeland, R.; Lopez-Burillo, S.; Mayo, J.C.; Sainz, R.M.; Reiter, R.J., Melatonin: A hormone, a tissue factor, an autocoid, a paracoid, and an antioxidant vitamin. J. Pineal Res. 2003, 34, 75-78.
2. Reiter, R.J., The melatonin rhythm: Both a clock and a calendar. Experientia 1993, 49, 654-664.
3. Malpaux, B.; Migaud, M.; Tricoire, H.; Chemineau, P. Biology of mammalian photoperiodism and the critical role of the pineal gland and melatonin. J. Biol. Rhythms 2001, 16, 336-347.
4. Maldonado, M.D.; Murillo-Cabezas, F.; Terron, M.P.; Flores, L.J.; Tan, D.X.; Manchester, L.C.; Reiter, R.J. The potential of melatonin in reducing morbidity-mortality after craniocerebral trauma. J. Pineal Res. 2007, 42, 1-11.
5. Peyrot, F.; Ducrocq, C. Potential role of tryptophan derivatives in stress responses characterized by the generation of reactive oxygen and nitrogen species. J. Pineal Res. 2008, 45, 235-246.
6. Reiter, R.J.; Tan, D.X.; Terron, M.P.; Flores, L.J.; Czarnocki, Z. Melatonin and its metabolites: New findings regarding their production and their radical scavenging actions. Acta Biochim. Pol. 2007, 54, 1-9.
7. Reiter, R.J. Pineal melatonin: Cell biology of its synthesis and of its physiological interactions. Endocr. Rev. 1991, 12, 151-180.
8. Tan, D.X.; Manchester, L.C.; Reiter, R.J.; Plummer, B.F.; Hardies, L.J.; Weintraub, S.T.; Vijayalaxmi Shepherd, A.M. A novel melatonin metabolite, cyclic 3-hydroxymelatonin: A biomarker of in vivo hydroxyl radical generation. Biochem. Biophys. Res. Commun. 1998, 253, 614-620.
9. Bubenik, G.A. Thirty four years since the discovery of gastrointestinal melatonin. J. Physiol. Pharmacol. 2008, 59, S33-S51.
10. Jaworek, J.; Brzozowski, T.; Konturek, S.J. Melatonin as an organoprotector in the stomach and the pancreas. J. Pineal Res. 2005, 38, 73-83.
11. Stefulj, J.; Hortner, M.; Ghosh, M.; Schauenstein, K.; Rinner, I.; Wolfler, A.; Semmler, J.; Liebmann, P.M. Gene expression of the key enzymes of melatonin synthesis in extrapineal tissues of the rat. J. Pineal Res. 2001, 30, 243-247.
12. Gomez-Corvera, A.; Cerrillo, I.; Molinero, P.; Naranjo, M.C.; Lardone, P.J.; Sanchez-Hidalgo, M.; Carrascosa-Salmoral, M.P.; Medrano-Campillo, P.; Guerrero, J.M.; Rubio, A. Evidence of immune system melatonin production by two pineal melatonin deficient mice, C57BL/6 and Swiss strains. J. Pineal Res. 2009, 47, 15-22.
13. Carrillo-Vico, A.; Calvo, J.R.; Abreu, P.; Lardone, P.J.; Garcia-Maurino, S.; Reiter, R.J.; Guerrero, J.M. Evidence of melatonin synthesis by human lymphocytes and its physiological significance: Possible role as intracrine, autocrine, and/or paracrine substance. FASEB J. 2004, 18, 537-539.
14. Conti, A.; Conconi, S.; Hertens, E.; Skwarlo-Sonta, K.; Markowska, M.; Maestroni, J.M. Evidence for melatonin synthesis in mouse and human bone marrow cells. J. Pineal Res. 2000, 28, 193-202.
15. Naranjo, M.C.; Guerrero, J.M.; Rubio, A.; Lardone, P.J.; Carrillo-Vico, A.; Carrascosa-Salmoral, M.P.; Jimenez-Jorge, S.; Arellano, M.V.; Leal-Noval, S.R.; Leal, M., et al. Melatonin biosynthesis in the thymus of humans and rats. Cell. Mol. Life Sci. 2007, 64, 781-790.
16. Carrillo-Vico, A.; Guerrero, J.M.; Lardone, P.J.; Reiter, R.J. A review of the multiple actions of melatonin on the immune system. Endocrine 2005, 27, 189-200.
17. Garcia-Maurino, S.; Gonzalez-Haba, M.G.; Calvo, J.R.; Rafii-El-Idrissi, M.; Sanchez-Margalet, V.; Goberna, R.; Guerrero, J.M. Melatonin enhances IL-2, IL-6, and IFN-gamma production by human circulating CD4+ cells: A possible nuclear receptor-mediated mechanism involving T helper type 1 lymphocytes and monocytes. J. Immunol. 1997, 159, 574-581.
18. Pozo, D.; Delgado, M.; Fernandez-Santos, J.M.; Calvo, J.R.; Gomariz, R.P.; Martin-Lacave, I.; Ortiz, G.G.; Guerrero, J.M. Expression of the Mel1a-melatonin receptor mRNA in T and B subsets of lymphocytes from rat thymus and spleen. FASEB J. 1997, 11, 466-473.
19. Pioli, C.; Caroleo, M.C.; Nistico, G.; Doria, G. Melatonin increases antigen presentation and amplifies specific and non specific signals for T-cell proliferation. Int. J. Immunopharmacol. 1993, 15, 463-468.
20. Currier, N.L.; Sun, L.Z.; Miller, S.C. Exogenous melatonin: Quantitative enhancement in vivo of cells mediating non-specific immunity. J. Neuroimmunol. 2000, 104, 101-108.
21. Garcia-Maurino, S.; Gonzalez-Haba, M.G.; Calvo, J.R.; Goberna, R.; Guerrero, J.M. Involvement of nuclear binding sites for melatonin in the regulation of IL-2 and IL-6 production by human blood mononuclear cells. J. Neuroimmunol. 1998, 92, 76-84.
22. Raghavendra, V.; Singh, V.; Kulkarni, S.K.; Agrewala, J.N. Melatonin enhances Th2 cell mediated immune responses: Lack of sensitivity to reversal by naltrexone or benzodiazepine receptor antagonists. Mol. Cell. Biochem. 2001, 221, 57-62.
23. Shaji, A.V.; Kulkarni, S.K.; Agrewala, J.N. Regulation of secretion of IL-4 and IgG1 isotype by melatonin-stimulated ovalbumin-specific T cells. Clin. Exp. Immunol. 1998, 111, 181-185.
24. Raghavendra, V.; Singh, V.; Shaji, A.V.; Vohra, H.; Kulkarni, S.K.; Agrewala, J.N. Melatonin provides signal 3 to unprimed CD4(+) T cells but failed to stimulate LPS primed B cells. Clin. Exp. Immunol. 2001, 124, 414-422.
25. Majewska, M.; Zajac, K.; Zemelka, M.; Szczepanik, M. Influence of melatonin and its precursor L-tryptophan on Th1 dependent contact hypersensitivity. J. Physiol. Pharmacol. 2007, 58, S125-S132.
26. Konakchieva, R.; Kyurkchiev, S.; Kehayov, I.; Taushanova, P.; Kanchev, L. Selective effect of methoxyindoles on the lymphocyte proliferation and melatonin binding to activated human lymphoid cells. J. Neuroimmunol. 1995, 63, 125-132.
27. Wang, H.; Wei, W.; Wang, N.P.; Gui, S.Y.; Wu, L.; Sun, W.Y.; Xu, S.Y. Melatonin ameliorates carbon tetrachloride-induced hepatic fibrogenesis in rats via inhibition of oxidative stress. Life Sci. 2005, 77, 1902-1915.
28. Lahiri, S.; Singh, P.; Singh, S.; Rasheed, N.; Palit, G.; Pant, K.K. Melatonin protects against experimental reflux esophagitis. J. Pineal Res. 2009, 46, 207-213.
29. Korhonen, R.; Lahti, A.; Kankaanranta, H.; Moilanen, E. Nitric oxide production and signaling in inflammation. Curr. Drug Targets 2005, 4, 471-479.
30. Szczepanik, M. Melatonin and its influence on immune system. J. Physiol. Pharmacol. 2007, 58, S115-S124.
31. Crespo, E.; Macias, M.; Pozo, D.; Escames, G.; Martin, M.; Vives, F.; Guerrero, J.M.; Acuna-Castroviejo, D. Melatonin inhibits expression of the inducible NO synthase II in liver and lung and prevents endotoxemia in lipopolysaccharide-induced multiple organ dysfunction syndrome in rats. FASEB J. 1999, 13, 1537-1546.
32. Jung, K.H.; Hong, S.W.; Zheng, H.M.; Lee, D.H.; Hong, S.S. Melatonin downregulates nuclear erythroid 2-related factor 2 and nuclear factor-kappaB during prevention of oxidative liver injury in a dimethylnitrosamine model. J. Pineal Res. 2009, 47, 173-183.
33. Veneroso, C.; Tunon, M.J.; Gonzalez-Gallego, J.; Collado, P.S. Melatonin reduces cardiac inflammatory injury induced by acute exercise. J. Pineal Res. 2009, 47, 184-191.
34. Lopez, L.C.; Escames, G.; Tapias, V.; Utrilla, P.; Leon, J.; Acuna-Castroviejo, D. Identification of an inducible nitric oxide synthase in diaphragm mitochondria from septic mice: Its relation with mitochondrial dysfunction and prevention by melatonin. Int. J. Biochem. Cell. Biol. 2006, 38, 267-278.
35. Escames, G.; Lopez, L.C.; Ortiz, F.; Lopez, A.; Garcia, J.A.; Ros, E.; Acuna-Castroviejo, D. Attenuation of cardiac mitochondrial dysfunction by melatonin in septic mice. FEBS J. 2007, 274, 2135-2147.
36. Lowes, D.A.; Almawash, A.M.; Webster, N.R.; Reid, V.L.; Galley, H.F. Melatonin and structurally similar compounds have differing effects on inflammation and mitochondrial function in endothelial cells under conditions mimicking sepsis. Br. J. Anaesth. 2011, 107, 193-201.
37. Lowes, D.A.; Webster, N.R.; Murphy, M.P.; Galley, H.F. Antioxidants that protect mitochondria reduce interleukin-6 and oxidative stress, improve mitochondrial function, and reduce biochemical markers of organ dysfunction in a rat model of acute sepsis. Br. J. Anaesth. 2013, 110, 472-480.
38. Tak, P.P.; Firestein, G.S. NF-κB: A key role in inflammatory diseases. J. Clin. Invest. 2001, 107, 7-11.
39. Chuang, J.I.; Mohan, N.; Meltz, M.L.; Reiter, R.J. Effect of melatonin on NF-kappa-B DNA-binding activity in the rat spleen. Cell. Biol. Int. 1996, 20, 687-692.
40. Bertuglia, S.; Marchiafava, P.L.; Colantuoni, A. Melatonin prevents ischemia reperfusion injury in hamster cheek pouch microcirculation. Cardiovasc. Res. 1996, 31, 947-952.
41. Sewerynek, E.; Reiter, R.J.; Melchiorri, D.; Ortiz, G.G.; Lewinski, A. Oxidative damage in the liver induced by ischemia-reperfusion: Protection by melatonin. Hepatogastroenterology 1996, 43, 898-905.
42. Reiter, R.J.; Calvo, J.R.; Karbownik, M.; Qi, W.; Tan, D.X. Melatonin and its relation to the immune system and inflammation. Ann. N. Y. Acad. Sci. 2000, 917, 376-86.
43. Gilad, E.; Wong, H.R.; Zingarelli, B.; Virag, L.; O'Connor, M.; Salzman, A.L.; Szabo, C. Melatonin inhibits expression of the inducible isoform of nitric oxide synthase in murine macrophages: Role of inhibition of NF-κB activation. FASEB J. 1998, 12, 685-693.
44. Li, Z.; Nickkholgh, A.; Yi, X.; Bruns, H.; Gross, M.L.; Hoffmann, K.; Mohr, E.; Zorn, M.; Buchler, M.W.; Schemmer, P. Melatonin protects kidney grafts from ischemia/reperfusion injury through inhibition of NF-κB and apoptosis after experimental kidney transplantation. J. Pineal Res. 2009, 46, 365-372.
45. Ozbek, E.; Ilbey, Y.O.; Ozbek, M.; Simsek, A.; Cekmen, M.; Somay, A. Melatonin attenuates unilateral ureteral obstruction-induced renal injury by reducing oxidative stress, iNOS, MAPK, and NF-κB expression. J. Endourol. 2009, 23, 1165-1173.
46. Pascua, P.; Camello-Almaraz, C.; Camello, P.J.; Martin-Cano, F.E.; Vara, E.; Fernandez-Tresguerres, J.A.; Pozo, M.J. Melatonin, and to a lesser extent growth hormone, restores colonic smooth muscle physiology in old rats. J. Pineal Res. 2011, 51, 405-415.
47. Yip, H.K.; Chang, Y.C.; Wallace, C.G.; Chang, L.T.; Tsai, T.H.; Chen, Y.L.; Chang, H.W.; Leu, S.; Zhen, Y.Y.; Tsai, C.Y., et al. Melatonin treatment improves adipose-derived mesenchymal stem cell therapy for acute lung ischemia-reperfusion injury. J. Pineal Res. 2013, 54, 207-221.
48. Qin, W.; Lu, W.; Li, H.; Yuan, X.; Li, B.; Zhang, Q.; Xiu, R. Melatonin inhibits IL1beta-induced MMP9 expression and activity in human umbilical vein endothelial cells by suppressing NF-κB activation. J. Endocrinol. 2012, 214, 145-153.
49. Xia, M.Z.; Liang, Y.L.; Wang, H.; Chen, X.; Huang, Y.Y.; Zhang, Z.H.; Chen, Y.H.; Zhang, C.; Zhao, M.; Xu, D.X., et al. Melatonin modulates TLR4-mediated inflammatory genes through MyD88-and TRIF-dependent signaling pathways in lipopolysaccharide-stimulated RAW264.7 cells. J. Pineal Res. 2012, 53, 325-334.
50. Lim, H.D.; Kim, Y.S.; Ko, S.H.; Yoon, I.J.; Cho, S.G.; Chun, Y.H.; Choi, B.J.; Kim, E.C. Cytoprotective and anti-inflammatory effects of melatonin in hydrogen peroxide-stimulated CHON-001 human chondrocyte cell line and rabbit model of osteoarthritis via the SIRT1 pathway. J. Pineal Res. 2012, 53, 225-237.
51. Choi, E.Y.; Jin, J.Y.; Lee, J.Y.; Choi, J.I.; Choi, I.S.; Kim, S.J., Melatonin inhibits prevotella intermedia lipopolysaccharide-induced production of nitric oxide and interleukin-6 in murine macrophages by suppressing NF-κB and STAT1 activity. J. Pineal Res. 2011, 50, 197-206.
52. Wang, J.; Xiao, X.; Zhang, Y.; Shi, D.; Chen, W.; Fu, L.; Liu, L.; Xie, F.; Kang, T.; Huang, W., et al. Simultaneous modulation of COX-2, p300, Akt, and Apaf-1 signaling by melatonin to inhibit proliferation and induce apoptosis in breast cancer cells. J. Pineal Res. 2012, 53, 77-90.
53. Shi, D.; Xiao, X.; Wang, J.; Liu, L.; Chen, W.; Fu, L.; Xie, F.; Huang, W.; Deng, W. Melatonin suppresses proinflammatory mediators in lipopolysaccharide-stimulated CRL1999 cells via targeting MAPK, NF-κB, c/EBPbeta, and p300 signaling. J. Pineal Res. 2012, 53, 154-165.
54. Marino, A.; Di Paola, R.; Crisafulli, C.; Mazzon, E.; Morabito, R.; Paterniti, I.; Galuppo, M.; Genovese, T.; La Spada, G.; Cuzzocrea, S. Protective effect of melatonin against the inflammatory response elicited by crude venom from isolated nematocysts of Pelagia noctiluca (Cnidaria, Scyphozoa). J. Pineal Res. 2009, 47, 56-69.
55. Kang, J.W.; Koh, E.J.; Lee, S.M. Melatonin protects liver against ischemia and reperfusion injury through inhibition of toll-like receptor signaling pathway. J. Pineal Res. 2011, 50, 403-411.
56. Wang, J.; Hao, H.; Yao, L.; Zhang, X.; Zhao, S.; Ling, E.A.; Hao, A.; Li, G. Melatonin suppresses migration and invasion via inhibition of oxidative stress pathway in glioma cells. J. Pineal Res. 2012, 53, 180-187.
57. Petrovsky, N.; Harrison, L.C. Diurnal rhythmicity of human cytokine production: A dynamic disequilibrium in T helper cell type 1/T helper cell type 2 balance? J. Immunol. 1997, 158, 5163-5168.
58. Garcia-Maurino, S.; Pozo, D.; Carrillo-Vico, A.; Calvo, J.R.; Guerrero, J.M. Melatonin activates Th1 lymphocytes by increasing IL-12 production. Life Sci. 1999, 65, 2143-2150.
59. Maestroni, G.J.; Conti, A.; Pierpaoli, W. Pineal melatonin, its fundamental immunoregulatory role in aging and cancer. Ann. N. Y. Acad. Sci. 1988, 521, 140-148.
60. Inserra, P.; Zhang, Z.; Ardestani, S.K.; Araghi-Niknam, M.; Liang, B.; Jiang, S.; Shaw, D.; Molitor, M.; Elliott, K.; Watson, R.R. Modulation of cytokine production by dehydroepiandrosterone (DHEA) plus melatonin (MLT) supplementation of old mice. Proc. Soc. Exp. Biol. Med. 1998, 218, 76-82.
61. Jung, F.J.; Yang, L.; Harter, L.; Inci, I.; Schneiter, D.; Lardinois, D.; Keel, M.; Weder, W.; Korom, S. Melatonin in vivo prolongs cardiac allograft survival in rats. J. Pineal Res. 2004, 37, 36-41.
62. Davidson, A.; Diamond, B. Autoimmune diseases. N. Engl. J. Med. 2001, 345, 340-350.
63. Steinman, L. Multiple sclerosis: A coordinated immunological attack against myelin in the central nervous system. Cell 1996, 85, 299-302.
64. Sospedra, M.; Martin, R. Immunology of multiple sclerosis. Annu. Rev. Immunol. 2005, 23, 683-747.
65. Ercolini, A.M.; Miller, S.D. Mechanisms of immunopathology in murine models of central nervous system demyelinating disease. J. Immunol. 2006, 176, 3293-3298.
66. Martin, R.; McFarland, H.F.; McFarlin, D.E. Immunological aspects of demyelinating diseases. Annu. Rev. Immunol. 1992, 10, 153-187.
67. Sobel, R.A.; Blanchette, B.W.; Bhan, A.K.; Colvin, R.B. The immunopathology of experimental allergic encephalomyelitis. I. Quantitative analysis of inflammatory cells in situ. J. Immunol. 1984, 132, 2393-2401.
68. Besler, H.T.; Comoglu, S. Lipoprotein oxidation, plasma total antioxidant capacity and homocysteine level in patients with multiple sclerosis. Nutr. Neurosci. 2003, 6, 189-196.
69. Glabinski, A.; Tawsek, N.S.; Bartosz, G. Increased generation of superoxide radicals in the blood of MS patients. Acta Neurol. Scand. 1993, 88, 174-177.
70. Hunter, M.I.; Nlemadim, B.C.; Davidson, D.L. Lipid peroxidation products and antioxidant proteins in plasma and cerebrospinal fluid from multiple sclerosis patients. Neurochem. Res. 1985, 10, 1645-1652.
71. MacMicking, J.D.; Willenborg, D.O.; Weidemann, M.J.; Rockett, K.A.; Cowden, W.B. Elevated secretion of reactive nitrogen and oxygen intermediates by inflammatory leukocytes in hyperacute experimental autoimmune encephalomyelitis: Enhancement by the soluble products of encephalitogenic T cells. J. Exp. Med. 1992, 176, 303-307.
72. Brass, S.D.; Duquette, P.; Proulx-Therrien, J.; Auerbach, S. Sleep disorders in patients with multiple sclerosis. Sleep. Med. Rev. 2010, 14, 121-129.
73. Melamud, L.; Golan, D.; Luboshitzky, R.; Lavi, I.; Miller, A. Melatonin dysregulation, sleep disturbances and fatigue in multiple sclerosis. J. Neurol. Sci. 2012, 314, 37-40.
74. Hedstrom, A.K.; Akerstedt, T.; Hillert, J.; Olsson, T.; Alfredsson, L. Shift work at young age is associated with increased risk for multiple sclerosis. Ann. Neurol. 2011, 70, 733-741.
75. Kang, J.C.; Ahn, M.; Kim, Y.S.; Moon, C.; Lee, Y.; Wie, M.B.; Lee, Y.J.; Shin, T. Melatonin ameliorates autoimmune encephalomyelitis through suppression of intercellular adhesion molecule-1. J. Vet. Sci. 2001, 2, 85-89.
76. Constantinescu, C.S.; Hilliard, B.; Ventura, E.; Rostami, A. Luzindole, a melatonin receptor antagonist, suppresses experimental autoimmune encephalomyelitis. Pathobiology 1997, 65, 190-194.
77. Dubocovich, M.L.; Yun, K.; Al-Ghoul, W.M.; Benloucif, S.; Masana, M.I. Selective MT2 melatonin receptor antagonists block melatonin-mediated phase advances of circadian rhythms. FASEB J. 1998, 12, 1211-1220.
78. Tsokos, G.C. Systemic lupus erythematosus. N. Engl. J. Med. 2011, 365, 2110-2121.
79. Kidd, P. Th1/Th2 balance: The hypothesis, its limitations, and implications for health and disease. Altern. Med. Rev. 2003, 8, 223-246.
80. Hayashi, T. Therapeutic strategies for SLE involving cytokines: Mechanism-oriented therapies especially IFN-gamma targeting gene therapy. J. Biomed. Biotechnol. 2010, 2010. doi:10.1155/2010/461641.
81. Wong, C.K.; Lit, L.C.; Tam, L.S.; Li, E.K.; Wong, P.T.; Lam, C.W. Hyperproduction of IL-23 and IL-17 in patients with systemic lupus erythematosus: Implications for Th17-mediated inflammation in auto-immunity. Clin. Immunol. 2008, 127, 385-393.
82. Lechner, O.; Dietrich, H.; Oliveira dos Santos, A.; Wiegers, G.J.; Schwarz, S.; Harbutz, M.; Herold, M.; Wick, G. Altered circadian rhythms of the stress hormone and melatonin response in lupus-prone MRL/MP-fas(Ipr) mice. J. Autoimmun. 2000, 14, 325-333.
83. Yin, Z.; Bahtiyar, G.; Zhang, N.; Liu, L.; Zhu, P.; Robert, M.E.; McNiff, J.; Madaio, M.P.; Craft, J. IL-10 regulates murine lupus. J. Immunol. 2002, 169, 2148-2155.
84. Jimenez-Caliani, A.J.; Jimenez-Jorge, S.; Molinero, P.; Fernandez-Santos, J.M.; Martin-Lacave, I.; Rubio, A.; Guerrero, J.M.; Osuna, C. Sex-dependent effect of melatonin on systemic erythematosus lupus developed in Mrl/Mpj-Faslpr mice: It ameliorates the disease course in females, whereas it exacerbates it in males. Endocrinology 2006, 147, 1717-1724.
85. Jimenez-Caliani, A.J.; Jimenez-Jorge, S.; Molinero, P.; Rubio, A.; Guerrero, J.M.; Osuna, C. Treatment with testosterone or estradiol in melatonin treated females and males MRL/MpJ-Faslpr mice induces negative effects in developing systemic lupus erythematosus. J. Pineal Res. 2008, 45, 204-211.
86. Zhou, L.L.; Wei, W.; Si, J.F.; Yuan, D.P. Regulatory effect of melatonin on cytokine disturbances in the pristane-induced lupus mice. Mediators Inflamm. 2010. doi:10.1155/2010/951210.
87. Wu, C.C.; Lu, K.C.; Lin, G.J.; Hsieh, H.Y.; Chu, P.; Lin, S.H.; Sytwu, H.K. Melatonin enhances endogenous heme oxygenase-1 and represses immune responses to ameliorate experimental murine membranous nephropathy. J. Pineal Res. 2012, 52, 460-469.
88. Choy, E.H.; Panayi, G.S. Cytokine pathways and joint inflammation in rheumatoid arthritis. N. Engl. J. Med. 2001, 344, 907-916.
89. Sulli, A.; Maestroni, G.J.; Villaggio, B.; Hertens, E.; Craviotto, C.; Pizzorni, C.; Briata, M.; Seriolo, B.; Cutolo, M. Melatonin serum levels in rheumatoid arthritis. Ann. N. Y. Acad. Sci. 2002, 966, 276-283.
90. Cutolo, M.; Straub, R.H. Circadian rhythms in arthritis: Hormonal effects on the immune/inflammatory reaction. Autoimmun. Rev. 2008, 7, 223-228.
91. Cutolo, M.; Balleari, E.; Giusti, M.; Monachesi, M.; Accardo, S. Sex hormone status of male patients with rheumatoid arthritis: Evidence of low serum concentrations of testosterone at baseline and after human chorionic gonadotropin stimulation. Arthritis Rheum. 1988, 31, 1314-1317.
92. Valenti, S.; Giusti, M. Melatonin participates in the control of testosterone secretion from rat testis: An overview of our experience. Ann. N. Y. Acad. Sci. 2002, 966, 284-289.
93. Forrest, C.M.; Mackay, G.M.; Stoy, N.; Stone, T.W.; Darlington, L.G. Inflammatory status and kynurenine metabolism in rheumatoid arthritis treated with melatonin. Br. J. Clin. Pharmacol. 2007, 64, 517-526.
94. Hansson, I.; Holmdahl, R.; Mattsson, R. Constant darkness enhances autoimmunity to type II collagen and exaggerates development of collagen-induced arthritis in DBA/1 mice. J. Neuroimmunol. 1990, 27, 79-84.
95. Hansson, I.; Holmdahl, R.; Mattsson, R., The pineal hormone melatonin exaggerates development of collagen-induced arthritis in mice. J. Neuroimmunol. 1992, 39, 23-30.
96. Hansson, I.; Holmdahl, R.; Mattsson, R. Pinealectomy ameliorates collagen II-induced arthritis in mice. Clin. Exp. Immunol. 1993, 92, 432-436.
97. Chen, Q.; Wei, W. Effects and mechanisms of melatonin on inflammatory and immune responses of adjuvant arthritis rat. Int. Immunopharmacol. 2002, 2, 1443-1449.
98. Bang, J.; Chang, H.W.; Jung, H.R.; Cho, C.H.; Hur, J.A.; Lee, S.I.; Choi, T.H.; Kim, S.H.; Ha, E. Melatonin attenuates clock gene cryptochrome1, which may aggravate mouse anti-type II collagen antibody-induced arthritis. Rheumatol. Int. 2012, 32, 379-385.
99. Jimenez-Caliani, A.J.; Jimenez-Jorge, S.; Molinero, P.; Guerrero, J.M.; Fernandez-Santos, J.M.; Martin-Lacave, I. Osuna, C. Dual effect of melatonin as proinflammatory and antioxidant in collagen-induced arthritis in rats. J. Pineal Res. 2005, 38, 93-99.
100. Kawasaki, E.; Abiru, N.; Eguchi, K. Prevention of type 1 diabetes: From the view point of beta cell damage. Diabetes Res. Clin. Pract. 2004, 66, S27-S32.
101. Aoki, C.A.; Borchers, A.T.; Ridgway, W.M.; Keen, C.L.; Ansari, A.A.; Gershwin, M.E. NOD mice and autoimmunity. Autoimmun. Rev. 2005, 4, 373-379.
102. Wicker, L.S.; Todd, J.A.; Peterson, L.B. Genetic control of autoimmune diabetes in the NOD mouse. Annu. Rev. Immunol. 1995, 13, 179-200.
103. Fox, H.S. Androgen treatment prevents diabetes in nonobese diabetic mice. J. Exp. Med. 1992, 175, 1409-1412.
104. Liblau, R.S.; Singer, S.M.; McDevitt, H.O. Th1 and Th2 CD4+ T cells in the pathogenesis of organ-specific autoimmune diseases. Immunol. Today 1995, 16, 34-38.
105. Hung, J.T.; Liao, J.H.; Lin, Y.C.; Chang, H.Y.; Wu, S.F.; Chang, T.H.; Kung, J.T.; Hsieh, S.L.; McDevitt, H.; Sytwu, H.K. Immunopathogenic role of TH1 cells in autoimmune diabetes: Evidence from a T1 and T2 doubly transgenic non-obese diabetic mouse model. J. Autoimmun. 2005, 25, 181-192.
106. Koarada, S.; Wu, Y.; Olshansky, G.; Ridgway, W.M. Increased nonobese diabetic Th1:Th2 (IFN-gamma:IL-4) ratio is CD4+ T cell intrinsic and independent of APC genetic background. J. Immunol. 2002, 169, 6580-6587.
107. Debray-Sachs, M.; Carnaud, C.; Boitard, C.; Cohen, H.; Gresser, I.; Bedossa, P.; Bach, J.F. Prevention of diabetes in NOD mice treated with antibody to murine IFN gamma. J. Autoimmun. 1991, 4, 237-248.
108. Campbell, I.L.; Kay, T.W.; Oxbrow, L.; Harrison, L.C. Essential role for interferon-gamma and interleukin-6 in autoimmune insulin-dependent diabetes in NOD/Wehi mice. J. Clin. Invest. 1991, 87, 739-742.
109. Cameron, M.J.; Arreaza, G.A.; Zucker, P.; Chensue, S.W.; Strieter, R.M.; Chakrabarti, S.; Delovitch, T.L. IL-4 prevents insulitis and insulin-dependent diabetes mellitus in nonobese diabetic mice by potentiation of regulatory T helper-2 cell function. J. Immunol. 1997, 159, 4686-4692.
110. Pennline, K.J.; Roque-Gaffney, E.; Monahan, M. Recombinant human IL-10 prevents the onset of diabetes in the nonobese diabetic mouse. Clin. Immunol. Immunopathol. 1994, 71, 169-175.
111. Peschke, E. Melatonin, endocrine pancreas and diabetes. J. Pineal Res. 2008, 44, 26-40.
112. Peschke, E.; Wolgast, S.; Bazwinsky, I.; Ponicke, K.; Muhlbauer, E. Increased melatonin synthesis in pineal glands of rats in streptozotocin induced type 1 diabetes. J. Pineal Res. 2008, 45, 439-448.
113. Stumpf, I.; Muhlbauer, E.; Peschke, E. Involvement of the cGMP pathway in mediating the insulin-inhibitory effect of melatonin in pancreatic beta-cells. J. Pineal Res. 2008, 45, 318-327.
114. Ramracheya, R.D.; Muller, D.S.; Squires, P.E.; Brereton, H.; Sugden, D.; Huang, G.C.; Amiel, S.A.; Jones, P.M.; Persaud, S.J. Function and expression of melatonin receptors on human pancreatic islets. J. Pineal Res. 2008, 44, 273-279.
115. Conti, A.; Maestroni, G.J. Role of the pineal gland and melatonin in the development of autoimmune diabetes in non-obese diabetic mice. J. Pineal Res. 1996, 20, 164-172.
116. Okitsu, T.; Bartlett, S.T.; Hadley, G.A.; Drachenberg, C.B.; Farney, A.C. Recurrent autoimmunity accelerates destruction of minor and major histoincompatible islet grafts in nonobese diabetic (NOD) mice. Am. J. Transplant. 2001, 1, 138-145.
117. Young, H.Y.; Zucker, P.; Flavell, R.A.; Jevnikar, A.M.; Singh, B. Characterization of the role of major histocompatibility complex in type 1 diabetes recurrence after islet transplantation. Transplantation 2004, 78, 509-515.
118. Sibley, R.K.; Sutherland, D.E.; Goetz, F.; Michael, A.F. Recurrent diabetes mellitus in the pancreas iso-and allograft. A light and electron microscopic and immunohistochemical analysis of four cases. Lab. Invest. 1985, 53, 132-144.
119. Tyden, G.; Reinholt, F.P.; Sundkvist, G.; Bolinder, J. Recurrence of autoimmune diabetes mellitus in recipients of cadaveric pancreatic grafts. N. Engl. J. Med. 1996, 335, 860-863.
120. Gysemans, C.A.; Waer, M.; Valckx, D.; Laureys, J.M.; Mihkalsky, D.; Bouillon, R.; Mathieu, C. Early graft failure of xenogeneic islets in NOD mice is accompanied by high levels of interleukin-1 and low levels of transforming growth factor-beta mRNA in the grafts. Diabetes 2000, 49, 1992-1997.
121. Sapmaz, E.; Ayar, A.; Celik, H.; Sapmaz, T.; Kilic, N.; Yasar, M.A. Effects of melatonin and oxytetracycline in autologous intraperitoneal ovary transplantation in rats. Neuro Endocrinol. Lett. 2003, 24, 350-354.
122. Lin, G.J.; Huang, S.H.; Chen, Y.W.; Hueng, D.Y.; Chien, M.W.; Chia, W.T.; Chang, D.M.; Sytwu, H.K. Melatonin prolongs islet graft survival in diabetic NOD mice. J. Pineal Res. 2009, 47, 284-292.
123. Zhang, Y.C.; Pileggi, A.; Agarwal, A.; Molano, R.D.; Powers, M.; Brusko, T.; Wasserfall, C.; Goudy, K.; Zahr, E.; Poggioli, R., et al. Adeno-associated virus-mediated IL-10 gene therapy inhibits diabetes recurrence in syngeneic islet cell transplantation of NOD mice. Diabetes 2003, 52, 708-716.
124. Kim, Y.H.; Lim, D.G.; Wee, Y.M.; Kim, J.H.; Yun, C.O.; Choi, M.Y.; Park, Y.H.; Kim, S.C.; Han, D.J. Viral IL-10 gene transfer prolongs rat islet allograft survival. Cell Transplant. 2008, 17, 609-618.
125. Abraham, C.; Cho, J.H. Inflammatory bowel disease. N. Engl. J. Med. 2009, 361, 2066-2078.
126. Strober, W.; Fuss, I.J.; Blumberg, R.S. The immunology of mucosal models of inflammation. Annu. Rev. Immunol. 2002, 20, 495-549.
127. Sartor, R.B. Mechanisms of disease: Pathogenesis of Crohn's disease and ulcerative colitis. Nat. Clin. Pract. Gastroenterol. Hepatol. 2006, 3, 390-407.
128. Neurath, M.F.; Finotto, S. The many roads to inflammatory bowel diseases. Immunity 2006, 25, 189-191.
129. Fuss, I.J.; Neurath, M.; Boirivant, M.; Klein, J.S.; de la Motte, C.; Strong, S.A.; Fiocchi, C.; Strober, W. Disparate CD4+ lamina propria (LP) lymphokine secretion profiles in inflammatory bowel disease. Crohn's disease LP cells manifest increased secretion of IFN-gamma, whereas ulcerative colitis LP cells manifest increased secretion of IL-5. J. Immunol. 1996, 157, 1261-1270.
130. Barrett, J.C.; Hansoul, S.; Nicolae, D.L.; Cho, J.H.; Duerr, R.H.; Rioux, J.D.; Brant, S.R.; Silverberg, M.S.; Taylor, K.D.; Barmada, M.M., et al. Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. Nat. Genet. 2008, 40, 955-962.
131. Fujino, S.; Andoh, A.; Bamba, S.; Ogawa, A.; Hata, K.; Araki, Y.; Bamba, T.; Fujiyama, Y. Increased expression of interleukin 17 in inflammatory bowel disease. Gut 2003, 52, 65-70.
132. Elson, C.O.; Cong, Y.; Weaver, C.T.; Schoeb, T.R.; McClanahan, T.K.; Fick, R.B.; Kastelein, R.A. Monoclonal anti-interleukin 23 reverses active colitis in a T cell-mediated model in mice. Gastroenterology 2007, 132, 2359-2370.
133. Hue, S.; Ahern, P.; Buonocore, S.; Kullberg, M.C.; Cua, D.J.; McKenzie, B.S.; Powrie, F.; Maloy, K.J. Interleukin-23 drives innate and T cell-mediated intestinal inflammation. J. Exp. Med. 2006, 203, 2473-2483.
134. Pentney, P.T.; Bubenik, G.A. Melatonin reduces the severity of dextran-induced colitis in mice. J. Pineal Res. 1995, 19, 31-39.
135. Nosal'ova, V.; Zeman, M.; Cerna, S.; Navarova, J.; Zakalova, M. Protective effect of melatonin in acetic acid induced colitis in rats. J. Pineal Res. 2007, 42, 364-370.
136. Dong, W.G.; Mei, Q.; Yu, J.P.; Xu, J.M.; Xiang, L.; Xu, Y. Effects of melatonin on the expression of iNOS and COX-2 in rat models of colitis. World J. Gastroenterol. 2003, 9, 1307-1311.
137. Cuzzocrea, S.; Mazzon, E.; Serraino, I.; Lepore, V.; Terranova, M.L.; Ciccolo, A.; Caputi, A.P. Melatonin reduces dinitrobenzene sulfonic acid-induced colitis. J. Pineal Res. 2001, 30, 1-12.
138. Mazzon, E.; Esposito, E.; Crisafulli, C.; Riccardi, L.; Muia, C.; di Bella, P.; Meli, R.; Cuzzocrea, S., Melatonin modulates signal transduction pathways and apoptosis in experimental colitis. J. Pineal Res. 2006, 41, 363-373.
139. Esposito, E.; Mazzon, E.; Riccardi, L.; Caminiti, R.; Meli, R.; Cuzzocrea, S. Matrix metalloproteinase-9 and metalloproteinase-2 activity and expression is reduced by melatonin during experimental colitis. J. Pineal Res. 2008, 45, 166-173.
140. Necefli, A.; Tulumoglu, B.; Giris, M.; Barbaros, U.; Gunduz, M.; Olgac, V.; Guloglu, R.; Toker, G. The effect of melatonin on TNBS-induced colitis. Dig. Dis. Sci. 2006, 51, 1538-1545.
141. Li, J.H.; Yu, J.P.; Yu, H.G.; Xu, X.M.; Yu, L.L.; Liu, J.; Luo, H.S. Melatonin reduces inflammatory injury through inhibiting NF-κB activation in rats with colitis. Mediators Inflamm. 2005, 2005, 185-193.
142. Mei, Q.; Xu, J.M.; Xiang, L.; Hu, Y.M.; Hu, X.P.; Xu, Z.W. Change of nitric oxide in experimental colitis and its inhibition by melatonin in vivo and in vitro. Postgrad. Med. J. 2005, 81, 667-672.
143. Marquez, E.; Sanchez-Fidalgo, S.; Calvo, J.R.; la de Lastra, C.A.; Motilva, V. Acutely administered melatonin is beneficial while chronic melatonin treatment aggravates the evolution of TNBS-induced colitis. J. Pineal Res. 2006, 40, 48-55.
144. Chojnacki, C.; Wisniewska-Jarosinska, M.; Walecka-Kapica, E.; Klupinska, G.; Jaworek, J.; Chojnacki, J. Evaluation of melatonin effectiveness in the adjuvant treatment of ulcerative colitis. J. Physiol. Pharmacol. 2011, 62, 327-334.
145. Prud'homme, G.J. Gene therapy of autoimmune diseases with vectors encoding regulatory cytokines or inflammatory cytokine inhibitors. J. Gene Med. 2000, 2, 222-232.
146. Ruiz, P.A.; Shkoda, A.; Kim, S.C.; Sartor, R.B.; Haller, D. IL-10 gene-deficient mice lack TGF-beta/Smad-mediated TLR2 degradation and fail to inhibit proinflammatory gene expression in intestinal epithelial cells under conditions of chronic inflammation. Ann. N. Y. Acad. Sci. 2006, 1072, 389-394.
147. Balasa, B.; Van Gunst, K.; Jung, N.; Katz, J.D.; Sarvetnick, N. IL-10 deficiency does not inhibit insulitis and accelerates cyclophosphamide-induced diabetes in the nonobese diabetic mouse. Cell. Immunol. 2000, 202, 97-102.
148. Kuhn, R.; Lohler, J.; Rennick, D.; Rajewsky, K.; Muller, W. Interleukin-10-deficient mice develop chronic enterocolitis. Cell 1993, 75, 263-274.
149. Groux, H.; O'Garra, A.; Bigler, M.; Rouleau, M.; Antonenko, S.; de Vries, J.E.; Roncarolo, M.G. A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 1997, 389, 737-742.
150. Hardeland, R.; Pandi-Perumal, S.R. Melatonin, a potent agent in antioxidative defense: Actions as a natural food constituent, gastrointestinal factor, drug and prodrug. Nutr. Metab. 2005, 2, 22.
151. Kucukakin, B.; Lykkesfeldt, J.; Nielsen, H.J.; Reiter, R.J.; Rosenberg, J.; Gogenur, I. Utility of melatonin to treat surgical stress after major vascular surgery-A safety study. J. Pineal Res. 2008, 44, 426-431.
152. Gitto, E.; Pellegrino, S.; Gitto, P.; Barberi, I.; Reiter, R.J. Oxidative stress of the newborn in the pre-and postnatal period and the clinical utility of melatonin. J. Pineal Res. 2009, 46, 128-139.
153. Kennaway, D.J.; Seamark, R.F. Circulating levels of melatonin following its oral administration or subcutaneous injection in sheep and goats. Aust. J. Biol. Sci. 1980, 33, 349-353.
154. DeMuro, R.L.; Nafziger, A.N.; Blask, D.E.; Menhinick, A.M.; Bertino, J.S., Jr. The absolute bioavailability of oral melatonin. J. Clin. Pharmacol. 2000, 40, 781-784.
155. Jacob, S.; Poeggeler, B.; Weishaupt, J.H.; Siren, A.L.; Hardeland, R.; Bahr, M.; Ehrenreich, H. Melatonin as a candidate compound for neuroprotection in amyotrophic lateral sclerosis (ALS): High tolerability of daily oral melatonin administration in ALS patients. J. Pineal Res. 2002, 33, 186-187.
156. Weishaupt, J.H.; Bartels, C.; Polking, E.; Dietrich, J.; Rohde, G.; Poeggeler, B.; Mertens, N.; Sperling, S.; Bohn, M.; Huther, G., et al. Reduced oxidative damage in ALS by high-dose enteral melatonin treatment. J. Pineal Res. 2006, 41, 313-323.