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

Clin Exp Immunol. 2003 Feb;131(2):355-63. doi: 10.1046/j.1365-2249.2003.02052.x.


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.

MeSH terms

  • Adolescent
  • Antigens, CD / blood*
  • Arthritis, Juvenile / blood*
  • Autoantibodies / blood
  • Binding, Competitive
  • Biological Assay / methods
  • Biological Factors / blood*
  • C-Reactive Protein / metabolism
  • Child
  • Child, Preschool
  • Cytokine Receptor gp130
  • Humans
  • Interleukin-6 / blood*
  • Interleukin-6 / immunology
  • Membrane Glycoproteins / blood*
  • Protein Binding
  • Receptors, Interleukin-6 / blood*
  • Signal Transduction
  • Solubility


  • Antigens, CD
  • Autoantibodies
  • Biological Factors
  • IL6ST protein, human
  • Interleukin-6
  • Membrane Glycoproteins
  • Receptors, Interleukin-6
  • Cytokine Receptor gp130
  • C-Reactive Protein