Establishment of two interleukin 6 (B cell stimulatory factor 2/interferon beta 2)-dependent human bone marrow-derived myeloma cell lines.

Abstract

Two IL-6-dependent human multiple myeloma cell lines, ILKM2 and ILKM3, were established from the bone marrow of patients with IgG-K multiple myeloma. Both cell lines had the typical morphology and immunocytochemical features of myeloma cells. The surface phenotype of both cell lines was PCA-1+, OKT10+, CD10(J-5)-, CD19(B4)-, CD20(B1)-, CD21(B2)-, and OKIa-1-. A monoclonal cytoplasmic Ig, IgG-K or K L chain, was positive in ILKM2 or ILKM3, respectively. EBV nuclear antigen was negative in both cell lines. They proliferated in the presence of macrophages or macrophage-derived factors (MDF). Among the recombinant cytokines examined, IL-6 most strongly augmented the growth of both cell lines. The anti-IL-6 antibody completely inhibited the IL-6-dependent growth and almost completely inhibited the MDF- or purified MDF-dependent growth of both cell lines, ILKM2 and ILKM3 are now being maintained in the culture medium containing 2 ng/ml rIL-6. These results suggest that IL-6 produced by macrophages may play an important role in the growth of myeloma cells in vivo and that macrophages or IL-6 can be used for establishing human myeloma cell lines.

Serum levels of interleukin 6, a potent myeloma cell growth factor, as a reflect of disease severity in plasma cell dyscrasias.

“…Furthermore, the recent obtaining of IL-6-dependent human myeloma cell lines favors the paracrine hypothesis (5, and Klein, B., unpublished results). Whatever the mechanism, paracrine or autocrine, it is clear that IL-6 is a potent myeloma cell growth factor in vitro (4)(5)(6), mainly in patients with fulminating MM and proliferating myeloma cells in vivo (7). The …”

“…Recently, this cytokine was found to be a strong in vitro myeloma cell growth factor in humans (4)(5)(6). However, its presentation as an autocrine (4) or paracrine (5,6) growth factor remains controversial. Our recent studies have shown that this myeloma cell growth factor is overproduced in vitro in the bone marrow of patients with active multiple myeloma (MM; 6).'…”

Treatment of B-lymphoproliferative disorder with a monoclonal anti-interleukin-6 antibody in 12 patients: a multicenter phase 1-2 clinical trial

“…It plays an important role in the proliferation and maturation of B cells. [36][37][38][39] Overproduction of this cytokine is thought to be involved in the pathogenesis of lymphoid malignancies, high-grade B-cell lymphomas, 40,41 and myelomas [42][43][44] in particular. It has also been shown that IL-6 promotes the growth of EBV-infected B cells, 45,46 that patients with BLPD produce abnormally high levels of IL-6, 45,47 and that B-cell lines derived from BLPD express the p80 chain of the IL-6 receptor.…”

Agonist anti-gp130 transducer monoclonal antibodies are human myeloma cell survival and growth factors

“…5 This cytokine blocks the dexamethasone-induced apoptosis of fresh myeloma cells, 6,7 transiently stimulates their proliferation in vitro 8,9 and makes it possible to obtain IL-6-dependent human myeloma cell lines (HMCL) from patients with terminal disease. [10][11][12] IL-6 is part of a cytokine family comprising interleukin-11 (IL-11), leukemia inhibitory factor (LIF), oncostatin M (OSM) and ciliary neurotrophic factor (CNTF). 13 These cytokines all activate the common signal transducing subunit gp130.…”