High amounts of circulating interleukin (IL)-6 in the form of monomeric immune complexes during anti-IL-6 therapy. Towards a new methodology for measuring overall cytokine production in human in vivo

Eur J Immunol. 1992 Nov;22(11):2819-24. doi: 10.1002/eji.1830221110.


A patient with plasma cell leukemia was treated with anti-interleukin (IL)-6 monoclonal antibodies (mAb) for 2 months. Using chromatography on protein A-Sepharose, anti-murine-IgG-Sepharose, anti-IL-6-mAb-Sepharose and gel filtration at pH 2.3, we have demonstrated that the anti-IL-6 mAb, by preventing the binding of IL-6 to its cell membrane receptor and its renal elimination, has induced huge amounts of IL-6 to circulate in the form of monomeric immune complexes. By using this observation, we have developed a mathematical modelling that allows the determination of the overall daily production of IL-6 in this patient, which was in the range of 15 micrograms per day. Overall in vivo production of cytokines has never been evaluated in animals or in humans before.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / therapeutic use*
  • Antigen-Antibody Complex / analysis*
  • Humans
  • Hybridomas / immunology
  • Interleukin-6 / biosynthesis*
  • Interleukin-6 / blood
  • Interleukin-6 / immunology
  • Leukemia, Plasma Cell / therapy
  • Models, Biological


  • Antibodies, Monoclonal
  • Antigen-Antibody Complex
  • Interleukin-6