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
- PMID: 1425909
- DOI: 10.1002/eji.1830221110
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
Abstract
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.
Similar articles
-
Antibodies chaperone circulating IL-6. Paradoxical effects of anti-IL-6 "neutralizing" antibodies in vivo.J Immunol. 1993 Sep 15;151(6):3225-36. J Immunol. 1993. PMID: 8376777
-
Comparative activity of Sant7 and anti-IL-6, IL-6R monoclonal antibodies in a murine model of B-cell lymphoma.Cytokine. 2005 Sep 7;31(5):368-74. doi: 10.1016/j.cyto.2005.06.006. Cytokine. 2005. PMID: 16061391
-
Anti-cytokine antibodies as carrier proteins. Prolongation of in vivo effects of exogenous cytokines by injection of cytokine-anti-cytokine antibody complexes.J Immunol. 1993 Aug 1;151(3):1235-44. J Immunol. 1993. PMID: 8393043
-
Increased circulating interleukin-6 (IL-6) activity in endotoxin-challenged mice pretreated with anti-IL-6 antibody is due to IL-6 accumulated in antigen-antibody complexes.Eur J Immunol. 1993 Aug;23(8):2026-9. doi: 10.1002/eji.1830230846. Eur J Immunol. 1993. PMID: 8344369
-
Sensitization of human renal cell carcinoma cells to cis-diamminedichloroplatinum(II) by anti-interleukin 6 monoclonal antibody or anti-interleukin 6 receptor monoclonal antibody.Cancer Res. 1995 Feb 1;55(3):590-6. Cancer Res. 1995. PMID: 7834629
Cited by
-
Bazedoxifene as a Novel GP130 Inhibitor for Pancreatic Cancer Therapy.Mol Cancer Ther. 2016 Nov;15(11):2609-2619. doi: 10.1158/1535-7163.MCT-15-0921. Epub 2016 Aug 17. Mol Cancer Ther. 2016. PMID: 27535971 Free PMC article.
-
Endogenous interleukin 6 production in multiple myeloma patients treated with chimeric monoclonal anti-IL6 antibodies indicates the existence of a positive feed-back loop.J Clin Invest. 1996 Sep 15;98(6):1441-8. doi: 10.1172/JCI118932. J Clin Invest. 1996. PMID: 8823310 Free PMC article. Clinical Trial.
-
Administration of neutralizing antibodies to interleukin-6 (IL-6) reduces experimental autoimmune encephalomyelitis and is associated with elevated levels of IL-6 bioactivity in central nervous system and circulation.Mol Med. 1995 Nov;1(7):795-805. Mol Med. 1995. PMID: 8612202 Free PMC article.
-
Identification of cyclic peptides able to mimic the functional epitope of IgG1-Fc for human Fc gammaRI.FASEB J. 2009 Feb;23(2):575-85. doi: 10.1096/fj.08-117069. Epub 2008 Oct 28. FASEB J. 2009. PMID: 18957574 Free PMC article.
-
Interleukin-6 (IL-6) production in mice infected with Trypanosoma cruzi: effect of its paradoxical increase by anti-IL-6 monoclonal antibody treatment on infection and acute-phase and humoral immune responses.Infect Immun. 1994 Feb;62(2):692-6. doi: 10.1128/iai.62.2.692-696.1994. Infect Immun. 1994. PMID: 8300226 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources