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Overnight variations in cortisol, interleukin-6, tumor necrosis factor α and other cytokines in people with rheumatoid arthritis.
  1. Mark G Perry (mgperry{at}doctors.org.uk)
  1. Academic Rheumatology Unit, University of Bristol, United Kingdom
    1. David S Jessop (david.jessop{at}bristol.ac.uk)
    1. Henry Wellcome Laboratories for Integrated Neuroscience and Endocrinology, University of Bristol, United Kingdom
      1. Linda P Hunt (l.p.hunt{at}bristol.ac.uk)
      1. Dept of Clinical Sciences at South Bristol, University of Bristol, United Kingdom
        1. John R Kirwan (john.kirwan{at}bristol.ac.uk)
        1. Academic Rheumatology Unit, University of Bristol, United Kingdom

          Abstract

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

          Methods: Sixteen 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 IL-6 concentration rose significantly from 35pg/ml at 22:00 to 64pg/ml at 07:15 (repeated measures ANOVA P<0.001). The geometric mean cortisol concentration rose significantly overnight from 57ng/ml at 01:00 to 229ng/ml at 07:15 (repeated measures ANOVA P<0.001). Neither TNFα nor the other cytokines measured changed significantly. Using cubic regression modelling IL-6 began to rise before cortisol (range 0.01-4.83 hrs) in 8 participants and after cortisol (range 1.11-5.14 hrs) in 3 participants. In a random coefficient model including data from all participants, the estimated mean IL-6 value began to rise 3.05 hours before the estimated mean cortisol value, with the IL-6 peak occurring 0.70 hours before the cortisol peak.

          Conclusion: The mean IL-6 and cortisol concentrations showed a significant overnight variation. Neither TNFα nor the other cytokines measured changed significantly. In a random coefficient model IL-6 began to rise approximately 3 hours, and reached a peak about 40 minutes, before cortisol. These studies confirm that there are abnormalities in plasma cortisol and IL-6 concentrations and dynamics. They also link the overnight rise in IL-6 to the circadian variation in symptoms.

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