Abnormal regulation of interleukin 6 in systemic juvenile idiopathic arthritis

P. Pignatti, M. Vivarelli, C. Meazza, M. G. Rizzolo, A. Martini, F. De Benedetti

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1670-1676
Number of pages7
JournalJournal of Rheumatology
Volume28
Issue number7
Publication statusPublished - 2001

Keywords

  • Interleukin 10
  • Interleukin 6
  • Juvenile idiopathic arthritis
  • Polymorphism

ASJC Scopus subject areas

  • Rheumatology
  • Immunology

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