Interleukin-6 Inhibits Apoptosis of Malignant Plasma Cells

Cell Immunol. 1995 May;162(2):248-55. doi: 10.1006/cimm.1995.1076.

Abstract

Multiple myeloma (MM) is a slow-growing malignancy whose plasma cells express the BCL-2 antiapoptosis gene. It is also associated with high levels of interleukin-6 (IL-6), a cytokine that prevents programmed cell death (PCD) in other target cell types. We thus investigated the ability of MM cells to undergo PCD and the possible regulatory effects of IL-6. Four MM cell lines underwent PCD when exposed to serum starvation, doxorubicin (dox), etoposide (VP-16), or dexamethasone (dex). Apoptosis was confirmed by morphologic criteria and/or detection of endonucleosomal DNA fragmentation. The concentrations of dox, VP-16, and dex required for PCD were at least 10-fold greater than that required to inhibit proliferation. Addition of IL-6 (but not IL-1 beta, IL-4, IL-7, or IL-10) inhibited PCD of 8226 targets induced by serum starvation or dexamethasone in a concentration-dependent fashion. In contrast, it had no effect on PCD induced by dox or VP-16. Exposure of targets to IL-6 did not increase BCL-2 expression (it actually consistently decreased expression), suggesting IL-6's protection against apoptosis was not mediated by direct effects on BCL-2. Targets protected from PCD by IL-6 were still sensitive to serum starvation and dex-induced cytostasis, but, after reculturing in drug-free complete media, they reinitiated normal proliferation. These data suggest that high levels of IL-6 may contribute to expansion of myeloma clones by inhibiting apoptotic death.

MeSH terms

  • Apoptosis / drug effects*
  • Cell Line
  • DNA Damage
  • Dactinomycin / analogs & derivatives
  • Dactinomycin / pharmacology
  • Dexamethasone / pharmacology
  • Doxorubicin / pharmacology
  • Etoposide / pharmacology
  • Humans
  • In Vitro Techniques
  • Interleukin-6 / pharmacology*
  • Multiple Myeloma / pathology
  • Plasma Cells / cytology*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-bcl-2

Substances

  • Interleukin-6
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Dactinomycin
  • Etoposide
  • 7-aminoactinomycin D
  • Dexamethasone
  • Doxorubicin