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 INVIVO

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 mug per day. Overall in vivo production of cytokines has never been evaluated in animals or in humans before.