Skip to main content

Advertisement

Log in

Morning melatonin serum values do not correlate with disease activity in rheumatoid arthritis: a cross-sectional study

  • Original Article
  • Published:
Rheumatology International Aims and scope Submit manuscript

Abstract

Rheumatoid arthritis (RA), the most prevalent autoimmune arthritis worldwide, usually presents with a circannual manner and, meanwhile, follows a circadian rhythm for symptoms like morning stiffness. Therefore, association between RA and some hormones such as melatonin (MLT) and vitamin D, whose serum values are related to body circadian rhythms or seasonal variations, has become more noticeable recently. Since some studies proposed that RA patients show altered MLT circadian rhythms, especially in concordance with symptoms, in this research, we present the correlation between MLT serum values and RA disease activity score (DAS28ESR). The current cross-sectional study was carried out on 80 volunteers (60 patients and 20 healthy controls). Fifty percent of the participants in each group were sampled in cold, and the same percentage were sampled in warm seasons at 8 a.m. Disease activity was estimated utilizing DAS28ESR. Patients with possible known confounders of MLT secretion were excluded. A commercial MLT ELISA kit was employed to measure MLT. Statistical analysis was conducted by SPSS-11 software. This study outlined higher serum values of MLT in RA patients compared with controls (P = 0.006, z = −2.73). However, MLT did not correlate with DAS in patients (P = 0.45, r = −0.09). GLM analysis demonstrated that DAS28ESR, age, disease duration, medications, gender, and season of sampling had no influence on serum MLT. However, newly diagnosed RA patients presented higher MLT values than established ones (P = 0.03, t = −2.2). A cutoff point value of 23 pg/mL (63.3 % sensitivity and 90 % specificity) for MLT was computed between patients and controls. This study denoted that morning MLT serum values are higher in RA patients than in healthy volunteers. However, MLT and RA disease activity or other disease characteristics do not correlate. MLT serum values were higher in newly diagnosed RA patients than established ones.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Firestein GS (2003) Evolving concepts of rheumatoid arthritis. Nature 423:356–361

    Article  CAS  PubMed  Google Scholar 

  2. Firestein GS (2005) Immunologic mechanisms in the pathogenesis of rheumatoid arthritis. JCR 11:S39–S44

    PubMed  Google Scholar 

  3. Straub RH, Cutolo M (2007) Circadian rhythms in rheumatoid arthritis: implications for pathophysiology and therapeutic management. Arthritis Rheum 56:399–408

    Article  PubMed  Google Scholar 

  4. Cutolo M, Maestroni G, Otsa K et al (2005) Circadian melatonin and cortisol levels in rheumatoid arthritis patients in winter time: a north and south Europe comparison. Ann Rheum Dis 64:212–216

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Forrest CM, Mackay GM, Stoy N et al (2007) Inflammatory status and kynurenine metabolism in rheumatoid arthritis treated with melatonin. Br J Clin Pharmacol 64:517–526

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Cutolo M, Villaggio B, Candido F et al (1999) Melatonin influences interleukin-12 and nitric oxide production by primary cultures of rheumatoid synovial macrophages and THP-1 cellsa. Ann N Y Acad Sci 876:246–254

    Article  CAS  PubMed  Google Scholar 

  7. Cutolo M, Maestroni G (2005) The melatonin–cytokine connection in rheumatoid arthritis. Ann Rheum Dis 64:1109–1111

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Cutolo M, Villaggio B, Otsa K et al (2005) Altered circadian rhythms in rheumatoid arthritis patients play a role in the disease’s symptoms. Autoimmun Rev 4:497–502

    Article  CAS  PubMed  Google Scholar 

  9. Maestroni GJ, Sulli A, Pizzorni C et al (2002) Melatonin in rheumatoid arthritis. Ann N Y Acad Sci 966:271–275

    Article  CAS  PubMed  Google Scholar 

  10. Saraux A, Berthelot JM, Chalès G et al (2001) Ability of the American College of rheumatology 1987 criteria to predict rheumatoid arthritis in patients with early arthritis and classification of these patients 2 years later. Arthritis Rheum 44:2485–2491

    Article  CAS  PubMed  Google Scholar 

  11. Prevoo M, Van’t Hof M, Kuper H et al (1995) Modified disease activity scores that include twenty-eight-joint counts development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 38:44–48

    Article  CAS  PubMed  Google Scholar 

  12. Mayeda A, Mannon S, Hofstetter J et al (1998) Effects of indirect light and propranolol on melatonin levels in normal human subjects. Psychiatry Res 81:9–17

    Article  CAS  PubMed  Google Scholar 

  13. Wright KP Jr, Badia P, Myers BL et al (1997) Caffeine and light effects on nighttime melatonin and temperature levels in sleep-deprived humans. Brain Res 747(1):78–84

    Article  CAS  PubMed  Google Scholar 

  14. Maestroni GJ, Cardinali DP, Esquifino AI et al (2005) Does melatonin play a disease-promoting role in rheumatoid arthritis? J Neuroimmunol 158:106–111

    Article  CAS  PubMed  Google Scholar 

  15. Sulli A, Maestroni G, Villaggio B et al (2002) Melatonin serum levels in rheumatoid arthritis. Ann N Y Acad Sci 966:276–283

    Article  CAS  PubMed  Google Scholar 

  16. Hansson I, Holmdahl R, Mattsson R (1992) The pineal hormone melatonin exaggerates development of collagen-induced arthritis in mice. J Neuroimmunol 39:23–30

    Article  CAS  PubMed  Google Scholar 

  17. Korkmaz A (2008) Melatonin as an adjuvant therapy in patients with rheumatoid arthritis. Br J Clin Pharmacol 66:316–317

    Article  PubMed Central  PubMed  Google Scholar 

  18. Maestroni GJ, Otsa K, Cutolo M (2008) Melatonin treatment does not improve rheumatoid arthritis. Br J Clin Pharmacol 65:797–798

    Article  PubMed Central  PubMed  Google Scholar 

  19. Brzezinski A (1997) Melatonin in humans. N Engl J Med 336:186–195

    Article  CAS  PubMed  Google Scholar 

  20. Nah SS, Won HJ, Park HJ et al (2009) Melatonin inhibits human fibroblast-like synoviocyte proliferation via extracellular signal-regulated protein kinase/P21(CIP1)/P27(KIP1) pathways. J Pineal Res 47:70–74

    Article  CAS  PubMed  Google Scholar 

  21. El-Awady HM, El-Wakkad AS, Saleh MT et al (2007) Serum melatonin in juvenile rheumatoid arthritis: correlation with disease activity. Pak J Biol Sci 10:1471–1476

    Article  CAS  PubMed  Google Scholar 

  22. Waldhauser F, Weiszenbacher G, Tatzer E et al (1988) Alterations in nocturnal serum melatonin levels in humans with growth and aging. J Clin Endocrinol Metab 66:648–652

    Article  CAS  PubMed  Google Scholar 

  23. Cutolo M (2012) Chronobiology and the treatment of rheumatoid arthritis. Curr Opin Rheumatol 24:312–318

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This article was extracted from the thesis prepared by Mr. Seyyed-Reza Seyyed-Hoseini to fulfill the requirements needed for earning the Internal medicine specialty degree. The Research Council of Mashhad University of Medical Sciences, Mashhad, Iran, is appreciated for financially supporting this study Grant Number (89592). We are also grateful to all patients for their kind participation.

Conflict of interest

The authors had no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Maryam Sahebari.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Afkhamizadeh, M., Sahebari, M. & Seyyed-Hoseini, SR. Morning melatonin serum values do not correlate with disease activity in rheumatoid arthritis: a cross-sectional study. Rheumatol Int 34, 1145–1151 (2014). https://doi.org/10.1007/s00296-013-2930-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-013-2930-x

Keywords

Navigation