title: Pre-analytical and biological variability in circulating interleukin 6 in healthy subjects and patients with rheumatoid arthritis.
abstract: Interleukin (IL)-6, a key player in the inflammatory response, may be a useful biomarker in rheumatoid arthritis (RA). The aim was to determine analytical variability, a reference interval in healthy subjects, and long- and short-term variation in serum and plasma IL-6 in healthy subjects and RA patients. An enzyme-linked immunosorbent assay from R&D was used for determination of serum and plasma IL-6. The IL-6 concentration did not depend on the type of anticoagulant used or the 3-h time delay between sampling and processing or repeated freeze-thaw cycles. The median plasma and serum IL-6 in 318 healthy subjects were 1.3 pg ml(-1) (range 0.33-26) and 1.4 pg ml(-1) (range 0.25-23), respectively. The median coefficient of variation in plasma IL-6 in 27 healthy subjects during 1 month, and repeated after 6 and 12 months were 27%, 31% and 26%, respectively. No significant long-term changes were observed in serum IL-6 over a 3-year period (14%, p = 0.33). Exercise (cycling) increased serum IL-6 in healthy subjects but not in RA patients. In conclusion, circulating IL-6 is stable regarding sample handling and shows little variation over time. Changes in IL-6 concentrations > 60% (2 times the biological variation) are likely to reflect changes in disease activity and not only pre-analytical or normal biological variability.
authors.affiliation: Department of Rheumatology Q 107, Herlev Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark. surland@dadlnet.dk
authors.forename: Lene S
authors.initials: LS
authors.lastname: Knudsen
authors.forename: Ib J
authors.initials: IJ
authors.lastname: Christensen
authors.forename: Tine
authors.initials: T
authors.lastname: Lottenburger
authors.forename: Mads N
authors.initials: MN
authors.lastname: Svendsen
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Nielsen
authors.forename: Lone
authors.initials: L
authors.lastname: Nielsen
authors.forename: Kim
authors.initials: K
authors.lastname: Hørslev-Petersen
authors.forename: Jens E B
authors.initials: JE
authors.lastname: Jensen
authors.forename: Gina
authors.initials: G
authors.lastname: Kollerup
authors.forename: Julia S
authors.initials: JS
authors.lastname: Johansen
mesh_terms: D000293:Adolescent; D000328:Adult; D001172:Arthritis, Rheumatoid / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D001800:Blood Specimen Collection / Q000379:methods; D002940:Circadian Rhythm; D015444:Exercise / Q000502:physiology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012016:Reference Values
chemical_list: D015415:Biomarkers; D015850:Interleukin-6