title: Circadian rhythm of serum interleukin-6 in rheumatoid arthritis.
abstract: OBJECTIVE
  To test the hypothesis of a diurnal variation in circulating levels of interleukin-6 (IL-6) and/or tumour necrosis factor-alpha (TNF-alpha) in rheumatoid arthritis and other inflammatory connective tissue diseases.
  
  
  METHODS
  Serum levels of IL-6 and TNF-alpha were measured at three hour intervals from 7:30 to 22:30 in 48 patients with different rheumatic diseases as well as ten healthy controls. In four of the patients with rheumatoid arthritis, serum IL-6 levels were measured before and after one week of treatment with prednisolone 15-20 mg daily.
  
  
  RESULTS
  IL-6 and TNF-alpha could not be detected in serum from healthy controls. However, serum IL-6 levels were substantially increased in patients with rheumatoid arthritis. Furthermore, patients with rheumatoid arthritis showed a statistically significant circadian variation in levels of IL-6. Peak values appeared in the morning and low values in the afternoon and evening. In contrast, levels were low and stable in other connective tissue diseases. Levels of TNF-alpha were low in patients with rheumatoid arthritis and high in patients with other connective tissue diseases, but without circadian rhythm. After treatment with prednisolone, levels of serum IL-6 decreased significantly, but the circadian rhythm remained.
  
  
  CONCLUSIONS
  The circadian rhythm of circulating IL-6 might correspond to the circadian rhythm of symptoms in rheumatoid arthritis. The diurnal variation of IL-6, and possibly other cytokines, might explain the conflicting results previously reported on the inter-relationship between circulating IL-6 levels and disease activity in rheumatoid arthritis.
authors.affiliation: Department of Medicine, University Hospital, Uppsala, Sweden.
authors.forename: N G
authors.initials: NG
authors.lastname: Arvidson
authors.forename: B
authors.initials: B
authors.lastname: Gudbjörnsson
authors.forename: L
authors.initials: L
authors.lastname: Elfman
authors.forename: A C
authors.initials: AC
authors.lastname: Rydén
authors.forename: T H
authors.initials: TH
authors.lastname: Tötterman
authors.forename: R
authors.initials: R
authors.lastname: Hällgren
mesh_terms: D000328:Adult; D001168:Arthritis / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy; D002940:Circadian Rhythm / Q000502:physiology*; D003240:Connective Tissue Diseases / Q000097:blood; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D011239:Prednisolone