Interleukin-6 and renal cell cancer: production, regulation, and growth effects

Cancer Immunol Immunother. 1992;35(2):97-105. doi: 10.1007/BF01741856.


Interleukin-6 (IL-6) is a recently characterized pleiotropic cytokine with antitumor activity. We investigated the production of IL-6 by renal cell cancer (RCC) and the growth effects of IL-6 on RCC. Using immunoperoxidase staining, cytoplasmic IL-6 was detected in four of four renal tumor lines and in tumor cells from freshly nephrectomized RCC. We found that IL-6 mRNA was expressed at basal culture conditions by seven of ten RCC tumor lines tested. Biologically active IL-6, as measured by the B9 assay, was produced by all ten RCC tumor lines. The addition of tumor necrosis factor alpha (TNF alpha) significantly augmented the expression of IL-6 mRNA in five RCC tumor lines (P less than 0.05). The combination of interferon gamma IFN gamma and TNF alpha further enhanced the augmented IL-6 mRNA accumulation seen with TNF alpha alone (P less than 0.05). TNF alpha also significantly stimulated the production of biologically active IL-6 (P less than 0.01). Furthermore, IFN gamma and TNF alpha were found to enhance IL-6 bioactivity synergistically (P less than 0.05). The growth effects of IL-6 on RCC were also investigated in two experimental systems: IL-6 was found to stimulate proliferative responses in six of six RCC tumor lines as measured by thymidine-uptake assays; however, only one of six tumor lines displayed an increase in proliferative response of greater than 21% (113%). The growth effect of IL-6 was further tested in clonogenic assays. One of the tumor lines tested displayed an enhanced growth response of up to 200%. We conclude that IL-6 is produced by RCC; this production is enhanced by TNF alpha with synergistic effects seen with IFN gamma at both mRNA and protein levels. In turn, IL-6 may have a modest stimulatory growth effect on certain RCC tumor lines.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Blotting, Northern
  • Carcinoma, Renal Cell / metabolism*
  • Cell Division / drug effects
  • Colony-Forming Units Assay
  • Cytokines / pharmacology
  • Cytoplasm / metabolism
  • Humans
  • Immunoenzyme Techniques
  • Interferon-gamma / pharmacology
  • Interleukin-6 / biosynthesis*
  • Interleukin-6 / genetics
  • Interleukin-6 / pharmacology
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics
  • Recombinant Proteins
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / pharmacology


  • Cytokines
  • Interleukin-6
  • RNA, Messenger
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma