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Circadian melatonin and cortisol levels in rheumatoid arthritis patients in winter time: a north and south Europe comparison

M Cutolo¹, G J M Maestroni², K Otsa³, O Aakre³, B Villaggio¹, S Capellino¹, P Montagna¹, L Fazzuoli⁴, T Veldi³, T Peets³, E Hertens², A Sulli¹

¹ Division of Rheumatology, Department of Internal Medicine, University of Genova, Genova, Italy
² Cantonal Institute of Pathology, Locarno, Switzerland
³ Division of Rheumatology, Tallinn Central Hospital, Tallinn, Estonia
⁴ Division of Endocrinology, Department of Endocrinology, University of Genova

Correspondence to:
Correspondence to:
Professor M Cutolo
Division of Rheumatology, Department of Internal Medicine, University of Genova, Viale Benedetto XV,6, 16136 Genova, Italy; mcutolo{at}unige.it

Background: Altered functioning of the hypothalamic-pituitary-adrenal axis and altered melatonin production might modulate the circadian symptoms in patients with rheumatoid arthritis.

Objective: To investigate the influence of different winter photoperiods on the circadian rhythms of serum melatonin, cortisol, tumour necrosis factor (TNF), and interleukin 6 (IL6) in patients with rheumatoid arthritis from a north Europe country (Estonia) and a south Europe country (Italy).

Methods: The patients from Estonia (n = 19) and Italy (n = 7) had similar disease severity and duration and were compared with healthy age and sex matched controls in the two countries. Blood samples were collected during the period January to February at 8 pm, 10 pm, midnight, 2 am, 4 am, 6 am, 8 am, and 3 pm. Melatonin was measured by radioimmunoassay using ¹²⁵I-melatonin. Serum cortisol, TNF, and IL6 cytokines were assayed by standard methods.

Results: Higher circadian melatonin concentrations from 10 pm and an earlier peak were observed in Estonian patients than in their age and sex matched controls (p<0.01). Starting from midnight, melatonin concentrations were significantly higher in the Estonian patients than in the Italian patients. No significant differences were observed for serum cortisol. Serum TNF was higher (p<0.05) in Estonian patients than in their controls and was correlated with the melatonin levels.

Conclusions: In a north European country (Estonia), the circadian rhythm of serum concentrations of melatonin and TNF in patients with rheumatoid arthritis were significantly higher than in matched controls or in rheumatoid patients from a south Europe country (Italy).

Abbreviations: DAS, disease activity score; IL6, interleukin 6; TNF, tumour necrosis factor ; UVR, ultraviolet radiation

Keywords: TNF; circadian rhythm; rheumatoid arthritis; melatonin

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