Serum Melatonin Levels Related with Night Pain and High Disease Activity in Seronegative Spondyloarthritis Patients

Year 2020, Volume: 6 Issue: 4, 177 - 187, 31.12.2020

Cengiz Karacaer , Cemal Bes Erdinc Serin Mehmet Soy

Abstract

Aim: Circadian rhythms play a major role in regulation of human physiological functions. Many signs and symptoms of inflammatory arthritis, especially in rheumatoid arthritis (RA), show intra- and inter-day variations. We aimed to measure serum levels of melatonin (MLT), interferon gamma (IFNγ), interleukin-10 (IL-10) and cortisol and to investigate relation with clinical parameters in patients with seronegative spondyloarthritis (SPA).
Methods: The study was designed prospectively. 17 patients with SPA (9 patients with Anklyosing Sponylitis, 8 patients with psoriatic arthritis), 20 patients with RA and 20 healthy controls were included to study. Serum MLT, IFNγ, IL-10 and cortisol measurement were made in patients and healthy controls at 8 p.m., 3 a.m. and 8 a.m.
Results: We found that MLT values of SPA patients were statistically lower (p=0,017) than healthy groups at 3 a.m.. Level of cortisol in RA patients at 8 a.m. were significantly lower than SPA patient and healthy control groups (p=0.047 and p=0.006; respectively). Cortisol levels in SPA patients which is measured at 8 a.m. was significantly higher (p=0.001) than other measurement in day. There was also significant positive correlation between Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and MLT levels measured at 8:00 p.m. in patients with SPA (r=0.688; p=0.040).
Conclusion: Serum MLT levels well correlated with disease activity in SPA patients. Back pain which is seen midnight can be related to decrease in MLT secretion. Our findings suggests MLT have a role in pathogenesis of SPA but, it is need more detailed studies for explaining of this role of MLT in pathogenesis of SPA.

Keywords

Circadian rhythm, Melatonin, Rheumatoid arthritis, Spondylo-arthropathies, Hypothalamopituitary adrenal axis

Supporting Institution

Bolu Abant İzzet Baysal Üniversitesi Bilimsel Araştırma Projesi

Project Number

SRP NO: BAP-2008.08.03.281

Thanks

I would like to express my respects and thanks to my esteemed, Prof Dr. Mehmet Soy, Prof Dr. Cemal Bes, Prof Dr. Erdinç Serin, for their support and knowledge throughout this thesis study.

References

• 1. Karasek M, Winczyk K. Melatonin in humans. J PhysiolPharmacol. 2006;57:19–39. PMID:17218758
• 2. Cutolo M., Maestroni G.J.M. The melatonin-cytokine connection in rheumatoid arthritis. Annals of the Rheumatic Diseases 2005;64:1109-11. https://doi.org/10.1136/ard.2005.038588
• 3. Sulli, A., Maestroni, G.J. M., Vıllaggıo, B., Hertens, E. et. al., Melatonin serum levels in rheumatoid arthritis. Annals of the New York Academy of Sciences. 2002; 966:276–83. https://doi.org/10.1136/ard.2004.023416
• 4. Cutolo M., Masi AT. Circadian rhythms and arthritis. Rheum Dis Clin North Am; 2005;31:115-29. https://doi.org/10.1016/j.rdc.2004.09.005
• 5. Cutolo M., Villaggio B, Candido F, Valenti S, Giusti M, Felli L, Sulli A, AccardoS..Melatonin influences interleukin-12 and nitric oxide production by primary cultures of rheumatoid synovial macrophages and THP-1 cells. Ann N Y AcadSci 1999;876:246–54. doi:10.1111/j.1749-6632.1999.tb07645.x
• 6. Dougados M, van der Linden S, Juhlin R, Huitfeldt B, Amor B, Calin A, Cats A, Dijkmans B, Olivieri I, Pasero G, et al. The EuropenSpondyloarthropathy Study Group preliminary criteria for the classification of spondylarthropathy. Arthritis Rheum. 1991; 34:1218–27. PMID:1930310
• 7. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62:2569–81. https://doi.org/10.1002/art.27584
• 8. Smolen JS, Aletaha D, Barton A, Burmester GR, Emery P, Firestein GS, Kavanaugh A, McInnes IB, Solomon DH, Strand V, Yamamoto K. Rheumatoid arthritis.Nat Rev Dis Primers. 2018;8:18001. https://doi.org/10.1038/nrdp.2018.1
• 9. Atzeni F, Cazzola M, Benucci M, Di Franco M, Salaffi F, Sarzi-Puttini P. Chronic widespread pain in the spectrum of rheumatological diseases. Best Pract Res Clin Rheumatol. 2011;25:165–71. https://doi.org/10.1016/j.berh.2010.01.011
• 10. Maestroni, G. J., Cardinali, D. P., Esquifino, A. I., & Pandi-Perumal, S. R.. Does melatonin play a disease-promoting role in rheumatoid arthritis?. Journal of neuroimmunology 2005;158:106–11. https://doi.org/10.1016/j.jneuroim.2004.08.015
• 11. Senna MK, Olama SM, El-Arman M.Serum melatonin level in ankylosing spondylitis: is it increased in active disease? Rheumatol Int. 2012;32:3429-33. https://doi.org/10.1007/s00296-011-2197-z
• 12. Senel K, Baykal T, Melikoglu MA, Erdal A, Karatay S, Karakoc A, Ugur M. Serum melatonin levels in ankylosing spondilitis: correlation with disease activity. Rheumatol Int. 2011;31:61-63. https://doi.org/10.1007/s00296-009-1223-x
• 13. Akihiko M, Yasuhiko M, Tatsuo O, Nobuo H, Yoshiro S, Susami I, Yoshio T, Yasuo H, and Yuichi Y. Circadian rhythm of serum testosterone and its relation to sleep: comparison with the variation in serum luteinizing hormone, prolactin, and cortisol in normal men. J. Clin. Endocrinol. Metab. 1980; 51:1365–71. https://doi.org/10.1210/jcem-51-6-1365
• 14. RudwaleitM, SiegertS, YinZ, EickJ, ThielA, RadbruchA , SieperJ , BraunJ. Low T-cell production of TNFa and IFN g in ankylosing spondylitis: itsrelation to HLA-B27 and influence of the TNF–308 gene polymorphism. Ann Rheum Dis 2001; 60: 36–42. https://dx.doi.org/10.1136%2Fard.60.1.36
• 15. Claudepierre P, Rymer JC & Chevalier X. IL–10 plasma levels correlate with disease activity in spondyloarthropathy. J Rheumatol 1997; 24: 1659–61. PMID:9263174
• 16. Cutolo M, Maestroni G J M, Otsa K Circadian melatonin and cortisol levels in rheumatoid arthritis patients in winter time: a north and south Europe comparison. Ann Rheum Dis 2005;64:212-16. https://dx.doi.org/10.1136%2Fard.2004.023416
• 17. Peytrovsky N, Harrison LC. The chronobiology of human cytokine production. Int Rev Immunol 1998;16:635–49. PMID:9646180