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.
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.
Lu
Z Y
ZY
Laboratory for Immunological and Hematological Oncology, Nantes, France.
Brochier
J
J
Wijdenes
J
J
Brailly
H
H
Bataille
R
R
Klein
B
B
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000936:Antigen-Antibody Complex / Q000032:analysis*; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D007952:Leukemia, Plasma Cell / Q000628:therapy; D008954:Models, Biological
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D015850:Interleukin-6