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.