PMID- 8499642 OWN - NLM STAT- MEDLINE DCOM- 19930701 LR - 20210216 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 81 IP - 11 DP - 1993 Jun 1 TI - gamma-Interferon in multiple myeloma: inhibition of interleukin-6 (IL-6)-dependent myeloma cell growth and downregulation of IL-6-receptor expression in vitro. PG - 3076-82 AB - In multiple myeloma, malignant plasma cells from most patients with active disease proliferate spontaneously when cultured for 5 days in vitro. This spontaneous proliferation is related to the endogenous production of interleukin-6 (IL-6), the major myeloma-cell growth factor. A 50% inhibitory dose (100 U/mL) of human recombinant gamma-interferon (hr gamma-IFN) blocked the proliferation of myeloma cells almost completely in all 19 patients analyzed. This inhibition was not caused by suppression of endogenous IL-6 production and was also observed in the presence of an excess of hrIL-6. hr gamma-IFN was also completely inhibitory in four human myeloma cell lines (HMCL) whose growth is totally dependent on the addition of exogenous hrIL-6. This inhibition was associated with a 47% to 73% decrease in membrane IL-6-binding gp80 protein as well as with a 90% decrease in the amount of gp80 mRNA in HMCL. These results are in line with recent reports indicating that gamma-IFN inhibited several IL-6-dependent biologic processes. They suggest a need to reconsider why previous preliminary clinical trials failed to demonstrate a beneficial effect of gamma-IFN in multiple myeloma. FAU - Portier, M AU - Portier M AD - INSERM U291, Immunopathologie des Maladies Tumorales et Autoimmunes, Montpellier, France. FAU - Zhang, X G AU - Zhang XG FAU - Caron, E AU - Caron E FAU - Lu, Z Y AU - Lu ZY FAU - Bataille, R AU - Bataille R FAU - Klein, B AU - Klein B LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Interleukin-6) RN - 0 (Membrane Proteins) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Immunologic) RN - 0 (Receptors, Interleukin-6) RN - 0 (Recombinant Proteins) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Bone Marrow/pathology MH - Cell Division/drug effects MH - Cells, Cultured MH - Female MH - Gene Expression/drug effects MH - Humans MH - In Vitro Techniques MH - Interferon-gamma/*pharmacology/therapeutic use MH - Interleukin-6/biosynthesis MH - Leukemia, Plasma Cell/pathology MH - Male MH - Membrane Proteins/metabolism MH - Multiple Myeloma/*drug therapy/pathology MH - RNA, Messenger/genetics MH - Receptors, Immunologic/genetics/metabolism MH - Receptors, Interleukin-6 MH - Recombinant Proteins EDAT- 1993/06/01 00:00 MHDA- 1993/06/01 00:01 CRDT- 1993/06/01 00:00 PHST- 1993/06/01 00:00 [pubmed] PHST- 1993/06/01 00:01 [medline] PHST- 1993/06/01 00:00 [entrez] AID - S0006-4971(20)71551-X [pii] PST - ppublish SO - Blood. 1993 Jun 1;81(11):3076-82.