Article Text

Overnight variations in cortisol, interleukin 6, tumour necrosis factor α and other cytokines in people with rheumatoid arthritis
  1. M G Perry1,
  2. J R Kirwan1,
  3. D S Jessop2,
  4. L P Hunt3
  1. 1
    Academic Rheumatology Unit, University of Bristol, Bristol Royal Infirmary, Bristol, UK
  2. 2
    Henry Wellcome Laboratories for Integrated Neuroscience and Endocrinology, University of Bristol, Bristol
  3. 3
    Department of Clinical Sciences at South Bristol, University of Bristol, Bristol, UK
  1. Professor J R Kirwan, Academic Rheumatology Unit, Bristol Royal Infirmary, Marlborough Street, Bristol BS2 8HW, UK; John.Kirwan{at}


Objective: To investigate overnight variations in absolute values and patterns of cytokines including interleukin 6 (IL6) and tumour necrosis factor α (TNFα) in rheumatoid arthritis (RA), and to relate any changes to those occurring in blood cortisol.

Methods: A total of 16 people (8 female) with active RA and who had received no recent glucocorticoids were admitted overnight. Blood samples were obtained at 13 time points between 21.00 and 10.00.

Results: The geometric mean IL6 concentration rose significantly from 35 pg/ml at 22:00 to 64 pg/ml at 07:15 (repeated measures analysis of variance (ANOVA), p<0.001). The geometric mean cortisol concentration rose significantly overnight from 57 ng/ml at 01:00 to 229 ng/ml at 07:15 (repeated measures ANOVA, p<0.001). Neither TNFα nor the other cytokines measured changed significantly. Using cubic regression modelling IL6 began to rise before cortisol (range 0.01 to 4.83 h) in eight participants and after cortisol (range 1.11 to 5.14 h) in three participants. In a random coefficient model including data from all participants, the estimated mean IL6 value began to rise 3.05 h before the estimated mean cortisol value, with the IL6 peak occurring 0.70 h before the cortisol peak.

Conclusion: The mean IL6 and cortisol concentrations showed a significant overnight variation. Neither TNFα nor the other cytokines measured changed significantly. In a random coefficient model IL6 began to rise approximately 3 h, and reached a peak about 40 min, before cortisol. These studies confirm that there are abnormalities in plasma cortisol and IL6 concentrations and dynamics. The data also link the overnight rise in IL6 to the circadian variation in symptoms.

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Supplementary materials


  • Competing interests: None declared.

  • Funding: Funded by The Charitable Trusts for the United Bristol Hospitals, The Wellcome Trust, GlaxoSmithKline Ltd and in part through an unrestricted educational grant from Nitec Pharma AG.

  • Ethics approval: The study was approved by the United Bristol Healthcare NHS Trust (UBHT) Research Ethics Committee and complied with the Helsinki declaration.

  • The dataset, including all the cytokine measurements, is available on application to the authors.

    ▸ Supplementary tables 1–3 are published online only at