title: Effects of naproxen and sulphasalazine or methotrexate on hypothalamic-pituitary-adrenal axis activity in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  To study the effects of antirheumatic drugs on hypothalamic-pituitary-adrenal (HPA) axis activity in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  Twenty patients with recent-onset active RA were studied before antirheumatic treatment, after 2 weeks of naproxen, and after 5½ months of additional treatment with sulphasalazine or methotrexate. The results before treatment were compared with those obtained in 20 age and sex-matched healthy controls (HC). Activity of the HPA-axis was assessed under basal conditions and during insulin tolerance tests (ITT). The ex-vivo production of interleukin (IL)-1β, tumour necrosis factor-α (TNF-α) and IL-6 in whole blood samples was measured with and without stimulation by LPS.
  
  
  RESULTS
  At baseline, plasma ACTH and cortisol levels were not different between patients with RA and HC. The unstimulated production of IL-6 was significantly higher in RA patients than in HC. After 2 weeks of treatment with naproxen, urinary cortisol excretion decreased significantly (p=0.03), and the area under the curve for plasma cortisol during the ITT was significantly lower (p=0.015). The LPS stimulated production of IL-1β was significantly lower compared with baseline. After 6 months, basal plasma, salivary and urinary cortisol levels, and plasma cortisol and ACTH levels during the ITT, were all unchanged in comparison to the pre-treatment period. The unstimulated ex-vivo production of IL-1β was significantly lower than before treatment.
  
  
  CONCLUSIONS
  Our results suggest that the non-steroidal anti-inflammatory drug naproxen suppresses the HPA-axis in the first weeks of treatment. After 6 months, this suppressive effect is no longer present, suggesting the existence of adaptive mechanisms.
authors.affiliation: Rheumatology Centre, Sint Maartenskliniek, Nijmegen, The Netherlands. a.eijsbouts@maartenskliniek.nl
authors.forename: Agnes M M
authors.initials: AM
authors.lastname: Eijsbouts
authors.forename: Marlies J E
authors.initials: MJ
authors.lastname: Kempers
authors.forename: Frank H J
authors.initials: FH
authors.lastname: van den Hoogen
authors.forename: Roland F J M
authors.initials: RF
authors.lastname: Laan
authors.forename: A R M M
authors.initials: AR
authors.lastname: Hermus
authors.forename: H A
authors.initials: HA
authors.lastname: Ross
authors.forename: Fred C G J
authors.initials: FC
authors.lastname: Sweep
authors.forename: Leo B A
authors.initials: LB
authors.lastname: van de Putte
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D001786:Blood Glucose / Q000032:analysis; D016207:Cytokines / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000502:physiology; D007328:Insulin; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D009288:Naproxen / Q000627:therapeutic use*; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000502:physiology; D012460:Sulfasalazine / Q000627:therapeutic use*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001786:Blood Glucose; D016207:Cytokines; D007328:Insulin; D012460:Sulfasalazine; D009288:Naproxen; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone; D008727:Methotrexate