Cytokines and soluble cytokine receptor induction after IL-12 administration in cancer patients

Clin Exp Immunol. 2000 Jan;119(1):28-37. doi: 10.1046/j.1365-2249.2000.01112.x.


This study shows that subcutaneous administration of increasing doses of IL-12, once a week, in 21 cancer patients increased the expression of cytokine genes (interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), IP-10, MIG, IL-10, IL-4) in peripheral blood mononuclear cells even at very low doses (30 ng/kg). Surprisingly, no circulating TNF-alpha or IL-4 could be detected in the plasma of patients treated with IL-12. However, a marked increase of soluble IL-4 receptor was demonstrated in the plasma of five of the six patients studied, which may represent an additional mechanism by which IL-12 inhibits the development of the Th2 response in vivo. A marked decline of IFN-gamma and IP10 induction was recorded after repeated cycles of IL-12. In contrast, in most patients IL-12 increased IL-10 expression with no subsequent decrease during the course of therapy, and even an earlier peak of IL-10 induction at the 6th cycle. In addition, a constant up-regulation of serum soluble IFN-gamma receptor levels was observed after each cycle of IL-12 treatment with a delayed peak compared with the IFN-gamma peak. The constant rise of IL-10 and soluble IFN-gamma receptor during IL-12 therapy may therefore contribute to the inhibition of IFN-gamma activity detected after repeated cycles of IL-12. Lastly, a marked heterogeneity of cytokine induction was observed from one patient to another, which appeared to be independent of the dose of IL-12 administered. These data may lead to a better understanding of the biological activity of IL-12 and the in vivo mechanisms of its regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / blood
  • Base Sequence
  • Chemokine CXCL9
  • Chemokines / blood
  • Chemokines / genetics
  • Chemokines, CXC / blood
  • Chemokines, CXC / genetics
  • Cytokines / blood*
  • Cytokines / genetics
  • DNA Primers / genetics
  • Dose-Response Relationship, Drug
  • Gene Expression / drug effects
  • Humans
  • Intercellular Signaling Peptides and Proteins*
  • Interferon-gamma / blood
  • Interferon-gamma / genetics
  • Interleukin-10 / blood
  • Interleukin-10 / genetics
  • Interleukin-12 / administration & dosage
  • Interleukin-12 / therapeutic use*
  • Interleukin-4 / blood
  • Interleukin-4 / genetics
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / immunology*
  • Neovascularization, Pathologic / prevention & control
  • RNA, Messenger / blood
  • RNA, Messenger / genetics
  • Receptors, Cytokine / blood*
  • Receptors, Cytokine / genetics
  • Receptors, Interleukin-4 / blood
  • Receptors, Interleukin-4 / genetics
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / therapeutic use
  • Solubility
  • Th1 Cells / immunology
  • Th2 Cells / immunology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism


  • Antineoplastic Agents
  • CXCL9 protein, human
  • Chemokine CXCL9
  • Chemokines
  • Chemokines, CXC
  • Cytokines
  • DNA Primers
  • Intercellular Signaling Peptides and Proteins
  • RNA, Messenger
  • Receptors, Cytokine
  • Receptors, Interleukin-4
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma