High circulating levels of biologically inactive IL-6/SIL-6 receptor complexes in systemic juvenile idiopathic arthritis: Evidence for serum factors interfering with the binding to gp130

P. Pignatti, L. Ciapponi, P. Galle, M. B. Hansen, M. Massa, C. Meazza, G. Paonessa, D. Novick, G. Ciliberto, Alberto Martini, F. De Benedetti

Research output: Contribution to journalArticlepeer-review

Abstract

We previously demonstrated that high levels of IL-6/sIL-6R complexes are present in sera of patients with systemic juvenile idiopathic arthritis (s-JIA) and that the amount of IL-6 estimated in the IL-6/sIL-6R complexes is markedly higher than that measured by the B9 assay. Here, we show that two additional bioassays, employing human myeloma XG-1 cells and human hepatoma Hep3B cells, detected serum IL-6 levels similar to those measured by the B9 assay and approximately 10-fold lower than the IL-6 levels estimated to be present in the IL-6/sIL-6R complex. Using an assay for the measurement of the amount of circulating IL-6 complexed with the sIL-6R and available for binding to gp130 (gp130 binding activity), we show that the IL-6/gp130 binding activity is similar to that detected by the bioassays and again significantly lower than that estimated to be present in the IL-6/sIL-6R complex. Addition of recombinant human IL-6 (rhIL-6) to sera of patients or controls results in a markedly lower increase in the gp130 binding activity in patients than in controls. Moreover, sera from s-JIA patients inhibited in a dose dependent manner the gp130 binding activity assay. These results show that sera from patients with s-JIA contain a factor, or factors, that inhibit(s) the binding of the IL-6/sIL-6R complex to gp130. This inhibitory activity does not appear to be due to soluble gp130, C-reactive protein or autoantibodies to IL-6.

Original languageEnglish
Pages (from-to)355-363
Number of pages9
JournalClinical and Experimental Immunology
Volume131
Issue number2
DOIs
Publication statusPublished - Feb 1 2003

Keywords

  • gp130
  • IL-6/slL-6R complex
  • Interleukin-6

ASJC Scopus subject areas

  • Immunology

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