Interleukin-6 leads to interleukin-10 production in several human multiple myeloma cell lines. Does interleukin-10 enhance the proliferation of these cells?

Leuk Res. 2010 Jul;34(7):912-6. doi: 10.1016/j.leukres.2009.08.012. Epub 2009 Sep 16.

Abstract

Multiple myeloma (MM) is characterised as a malignant plasma cell proliferation. Interleukin-6 (IL-6) is an important cytokine in the proliferation of the multiple myeloma cells. Interleukin-10 (IL-10) is involved in the terminal differentiation of B cells into plasma cells and enhances the proliferation of B cells. Elevated IL-10 levels were detected in patients with MM, relating to the clinical manifestation of the disease. In this study it was investigated the effect of exogenous IL-6 on the IL-10 production and the proliferative effect of IL-6 and IL-10 in human multiple myeloma cell lines. The ten cell lines had different sources: blood, ascitic fluid, bone marrow, peritoneum and lymph node.

Results: (1) Four cell lines produced IL-10 (up to 179 pg/ml) spontaneously. IL-6 increased the IL-10 production up to 1626 pg/ml in 6/10 cell lines. With IL-6 receptor antagonist (IL-6RA) the values of IL-10 were in the range of untreated samples (spontaneous cytokine production). IL-6RA counteracted the increased IL-10 production induced by IL-6 treatment and decreased the high values of IL-10 significantly. (2) IL-6 enhanced the proliferation (up to 160%) in 9/10 cell lines, IL-10 enhanced the proliferation (up to 170%) in 7/10 cell lines. There was a significant correlation between the proliferative effects of IL-6 and IL-10.

Conclusion: It is reported for the first time that IL-6 leads to a marked production of IL-10 and that this cytokine is an IL-6 related growth factor for MM cells. The findings of this study can be important in the therapeutic modalities of multiple myeloma.

MeSH terms

  • Ascites / pathology
  • Bone Marrow / pathology
  • Cell Division / drug effects
  • Cell Line, Tumor / drug effects
  • Humans
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / genetics
  • Interleukin-10 / pharmacology*
  • Interleukin-6 / pharmacology*
  • Lymph Nodes / pathology
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / pathology*
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Paracrine Communication
  • Pleura / pathology
  • Receptors, Interleukin-6 / biosynthesis
  • Receptors, Interleukin-6 / drug effects
  • Receptors, Interleukin-6 / genetics
  • Recombinant Proteins / pharmacology

Substances

  • IL10 protein, human
  • IL6 protein, human
  • Interleukin-6
  • Neoplasm Proteins
  • Receptors, Interleukin-6
  • Recombinant Proteins
  • Interleukin-10