title: Revisiting IL-6 antagonism in multiple myeloma.
abstract: IL-6, a cytokine with broad functions in inflammation and immunity, has been extensively studied for its role on normal antibody-producing plasma cells. In addition, IL-6 is recognized as a proliferative factor for multiple myeloma (MM), a malignant plasma cell tumor developing in the bone marrow. Blocking IL-6 signaling was thus developed into a therapeutic approach for MM already early after its discovery, in 1991. Unfortunately, the first clinical trials did not demonstrate a clear benefit, but despite this apparent failure hopes on IL-6 antagonism are still high and trials ongoing. The cellular source of IL-6 has long been a matter of debate. IL-6 was first recognized as an autocrine factor produced by the malignant plasma cells themselves, but later reports clearly showed that IL-6 was a paracrine factor, produced by the microenvironment, mostly by cells from the myeloid lineage. Recently, we have confirmed that IL-6 originates from myeloid lineage cells, mainly from myeloid precursors. We have also demonstrated that IL-6 amplifies the pool of myeloid cells producing a second key factor for MM, a proliferation inducing ligand (APRIL). These findings form a new rationale for IL-6 inhibition in MM and for new ways to use IL-6 blocking in the clinics.
authors: Hematology Service and Service of Clinical Pathology, Geneva University Hospitals, Geneva, Switzerland. Electronic address: thomas.matthes@hcuge.ch.
authors: Thomas
authors: T
authors: Matthes
authors: Analytical Immunology for chronic pathologies, Albert Bonniot Institute, INSERM/University Joseph Fourier U823, Grenoble, France.
authors: Benoit
authors: B
authors: Manfroi
authors: Analytical Immunology for chronic pathologies, Albert Bonniot Institute, INSERM/University Joseph Fourier U823, Grenoble, France.
authors: Bertrand
authors: B
authors: Huard
mesh_terms: D001853:Bone Marrow / Q000276:immunology; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000276:immunology; D010950:Plasma Cells; D000093242:Interleukin-6 Inhibitors
chemical_list: D015850:Interleukin-6; D000093242:Interleukin-6 Inhibitors
keywords: APRIL; IL-6; Immunotherapy; Microenvironment; Multiple myeloma