Defective hypothalamic response to immune and inflammatory stimuli in patients with rheumatoid arthritis.
OBJECTIVE
To determine the integrity of the hypothalamic-pituitary-adrenal (HPA) axis responses to immune/inflammatory stimuli in patients with rheumatoid arthritis (RA).


METHODS
Diurnal secretion of cortisol and the cytokine and cortisol responses to surgery were studied in subjects with active RA, in subjects with chronic osteomyelitis (OM), and in subjects with noninflammatory arthritis, who served as controls.


RESULTS
Patients with RA had a defective HPA response, as evidenced by a diurnal cortisol rhythm of secretion which was at the lower limit of normal in contrast to those with OM, and a failure to increase cortisol secretion following surgery, despite high levels of interleukin-1 beta (IL-1 beta) and IL-6. The corticotropin-releasing hormone stimulation test in the RA patients showed normal results, thus suggesting a hypothalamic defect, but normal pituitary and adrenal function.


CONCLUSIONS
These findings suggest that RA patients have an abnormality of the HPA axis response to immune/inflammatory stimuli which may reside in the hypothalamus. This hypothalamic abnormality may be an additional, and hitherto unrecognized, factor in the pathogenesis of RA.
Chikanza
I C
IC
Division of Medicine, United Medical and Dental Schools of Guy's Hospital, London, United Kingdom.
Petrou
P
P
Kingsley
G
G
Chrousos
G
G
Panayi
G S
GS
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000503:physiopathology* / Q000601:surgery; D002940:Circadian Rhythm; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism; D007031:Hypothalamus / Q000503:physiopathology*; D007107:Immune System / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period
D016207:Cytokines; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone