TY - GEN
T1 - Effect of novel therapeutic glucocorticoids on circadian rhythms of hormones and cytokines in rheumatoid arthritis
T2 - Annals of the New York Academy of Sciences
AU - Kirwan, John R.
AU - Clarke, Lynsey
AU - Hunt, Linda P.
AU - Perry, Mark G.
AU - Straub, Rainer H.
AU - Jessop, David S.
PY - 2010/4
Y1 - 2010/4
N2 - The morning stiffness and pain of rheumatoid arthritis (RA) is accompanied by a rise in serum interleukin-6 (IL-6) from 2 am to 7 am. Using a formulation that releases prednisone at 2 am (after ingestion at 10 pm), we studied the circadian dynamics of serum IL-6, other cytokines, and cortisol in 9 patients before and after 2 weeks, therapy. Significant improvements occurred in morning stiffness, pain, disease activity, and the acute-phase response. Only IL-6 showed measurable cytokine circadian variation, its high pretreatment peak was abolished, and changes in IL-6 correlated with the changes in morning stiffness. Following treatment, afternoon and evening serum cortisol was reduced, but in the early morning cortisol peak concentration increased. Thus the severity of morning symptoms is related to nocturnal serum IL-6 concentration. The specific timing of the medication, linked to the interaction between IL-6 and the hypothalamic-pituitary-adrenal (HPA) axis, may correct a postulated deficiency in HPA control in RA.
AB - The morning stiffness and pain of rheumatoid arthritis (RA) is accompanied by a rise in serum interleukin-6 (IL-6) from 2 am to 7 am. Using a formulation that releases prednisone at 2 am (after ingestion at 10 pm), we studied the circadian dynamics of serum IL-6, other cytokines, and cortisol in 9 patients before and after 2 weeks, therapy. Significant improvements occurred in morning stiffness, pain, disease activity, and the acute-phase response. Only IL-6 showed measurable cytokine circadian variation, its high pretreatment peak was abolished, and changes in IL-6 correlated with the changes in morning stiffness. Following treatment, afternoon and evening serum cortisol was reduced, but in the early morning cortisol peak concentration increased. Thus the severity of morning symptoms is related to nocturnal serum IL-6 concentration. The specific timing of the medication, linked to the interaction between IL-6 and the hypothalamic-pituitary-adrenal (HPA) axis, may correct a postulated deficiency in HPA control in RA.
KW - Arthritis
KW - Cortisol
KW - IL-6
UR - http://www.scopus.com/inward/record.url?scp=77951251889&partnerID=8YFLogxK
U2 - 10.1111/j.1749-6632.2009.05289.x
DO - 10.1111/j.1749-6632.2009.05289.x
M3 - Conference proceedings published in a book
AN - SCOPUS:77951251889
SN - 9781573317696
T3 - Annals of the New York Academy of Sciences
SP - 127
EP - 133
BT - Neuroendocrine Immunology in Rheumatic Diseases
PB - Blackwell Publishing Inc.
ER -