Mean interleukin (IL)-6 and cortisol concentrations vary significantly throughout the night in patients with rheumatoid arthritis, UK researchers report.
“Patients with RA report joint pain, swelling and stiffness on waking, which improve as the morning progresses,” note John Kirwan (Bristol Royal Infirmary) and colleagues in the Annals of the Rheumatic Diseases.
“In RA synovitis is driven in part by excessive production of cytokines such as IL-6 and tumor necrosis factor-alpha (TNFα). The hypothalamic–pituitary–adrenal axis and its associated circadian variations in cortisol are also implicated,” they add.
To investigate overnight variations in absolute values and patterns of cytokines including IL-6 and tumor necrosis factor alpha (TNFα), as well as blood cortisol levels, Kirwan and team studied eight men and eight women with active RA.
The study participants, who had received no recent glucocorticoid treatment, were admitted to hospital overnight and blood samples were obtained at 13 time points between 21:00 h and 10:00 h.
Three healthy control volunteers were also investigated to ensure that blood sample collection did not disturb normal circadian variation.
The researchers note that the pattern of plasma cortisol variation in healthy volunteers was similar to that previously reported, while IL-6 levels remained low for most of the night but showed a small rise in the early hours of the morning.
In the patients with RA, the geometric mean IL-6 concentration rose significantly from 35 pg/ml at 22:00 h to 64 pg/ml at 07:15 h. The geometric mean cortisol concentration also rose significantly overnight from 57 ng/ml at 01:00 h to 229 ng/ml at 07:15 h.
Neither TNF-α nor the other cytokines measured changed significantly.
Using a random coefficient model, the researchers demonstrate that the estimated mean IL-6 value began to rise at 3.05 h before the estimated mean cortisol value, with the IL-6 peak occurring 0.70 h before the cortisol peak.
“These studies confirm that there are abnormalities in plasma cortisol and IL-6 concentrations and dynamics,” conclude Kirwan and co-authors.
“The data also link the overnight rise in IL-6 to the circadian variation in symptoms.”