Abnormal regulation of interleukin 6 in systemic juvenile idiopathic arthritis

J Rheumatol. 2001 Jul;28(7):1670-6.


Objective: To evaluate the in vitro production of interleukin 6 (IL-6) by peripheral blood mononuclear cells (PBMC) of patients with systemic juvenile idiopathic arthritis (JIA), its regulation by IL-10, and the association of abnormal regulation of IL-6 production with presence of polymorphisms in the regulatory sequence of the IL-6 gene.

Methods: PBMC were cultured in the absence or presence of lipopolysaccharide (LPS). IL-6 and IL-10 levels were measured by ELISA. Polymorphisms in the regulatory sequences of the IL-6 gene were assessed by restriction fragment length polymorphism analysis and sequencing of amplified regions.

Results: Patients' PBMC produced high amounts of IL-6 compared to controls in unstimulated conditions. The IL-10 50% inhibitory dose of LPS stimulated IL-6 production was significantly higher in patients than controls. IL-10 levels produced in the absence or presence of LPS were comparable between patients and controls. The -174 G/C polymorphism in the IL-6 gene does not appear to be correlated with the high unstimulated IL-6 production or with the reduced inhibition by IL-10 observed in patients with JIA. No differences in patients compared to controls and with respect to the published sequence were found in the 3' untranslated region (UTR) of the IL-6 gene.

Conclusion: Most patients with JIA have increased unstimulated production of IL-6 and reduced inhibition of IL-6 production by IL-10. This abnormal regulation of IL-6 production is not secondary to a defect in IL-10 production, and is not associated with polymorphism of alleles at position -174 of the 5' flanking region or with mutations in the 3' untranslated region of the IL-6 gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Adolescent
  • Arthritis, Juvenile / genetics
  • Arthritis, Juvenile / immunology*
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Humans
  • Interleukin-10 / metabolism
  • Interleukin-6 / genetics*
  • Interleukin-6 / metabolism*
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / immunology*
  • Polymorphism, Genetic


  • 3' Untranslated Regions
  • Interleukin-6
  • Interleukin-10