Interleukin-4 inhibits growth of multiple myelomas by suppressing interleukin-6 expression.
Unfractionated bone marrow (BM) cells obtained from patients with multiple myeloma (MM) exhibit high levels of interleukin (IL)-6. Secretion of IL-6 by these cells as well as spontaneous plasma cell proliferation can be abrogated by neutralizing anti-IL-6 monoclonal antibody (MoAb). Treatment of BM cells with recombinant human (rh)IL-4 at doses of 50 to 250 U/mL blocked endogenous IL-6 synthesis in a dose-dependent fashion and was associated with significant reduction of plasma cell growth that could be reversed by exogenous rhIL-6. Enrichment of BM cells from MM patients for plasma cells and adherent cells and analysis of IL-6 mRNA in these subpopulations by means of quantitative polymerase chain reaction (PCR) showed that adherent BM cells accounted for most of the synthesis of IL-6 transcripts, whereas plasma cells displayed negligible levels of IL-6 mRNA only. These results suggest therapeutic evaluation of rhIL-4 in patients with plasma cell neoplasms.
Herrmann
F
F
Department of Hematology and Oncology, University of Freiburg Medical Center, Germany.
Andreeff
M
M
Gruss
H J
HJ
Brach
M A
MA
Lübbert
M
M
Mertelsmann
R
R
D001483:Base Sequence; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000502:physiology*; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D015850:Interleukin-6; D015847:Interleukin-4