Effects of micro-environment- and malignant cell-derived interleukin-1 in carcinogenesis, tumour invasiveness and tumour-host interactions

Eur J Cancer. 2006 Apr;42(6):751-9. doi: 10.1016/j.ejca.2006.01.010. Epub 2006 Mar 10.


Interleukin-1 (IL-1) comprises a family of closely related genes; the two major agonistic proteins, IL-1alpha and IL-1beta, are pleiotropic and affect mainly inflammation, immunity and haemopoiesis. IL-1beta is active solely in its secreted form, whereas IL-1alpha is active mainly as an intracellular precursor. IL-1 is abundant at tumour sites, where it may affect the process of carcinogenesis, tumour growth and invasiveness and the patterns of tumour-host interactions. Here, we review the effects of micro-environment- and tumour cell-derived IL-1 on malignant processes in experimental tumour models. We propose that membrane-associated IL-1alpha expressed on malignant cells stimulates anti-tumour immunity, while secretable IL-1beta derived from the micro-environment or the malignant cells, activates inflammation that promotes invasiveness and induces tumour-mediated suppression. Inhibition of the function of IL-1 by the inhibitor of IL-1, interleukin-1 receptor antagonist (IL-1Ra), reduces tumour invasiveness and alleviates tumour-mediated suppression, pointing to its feasible use in cancer therapy. Differential manipulation of IL-1alpha and IL-1beta in malignant cells or in the tumour's micro-environment may open new possibilities for using IL-1 in cancer immunotherapy.

Publication types

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

MeSH terms

  • Animals
  • Carcinogens
  • Humans
  • Inflammation / complications*
  • Inflammation / immunology
  • Inflammation / pathology
  • Interleukin-1 / classification
  • Interleukin-1 / metabolism
  • Interleukin-1 / physiology*
  • Methylcholanthrene
  • Mice
  • Models, Biological
  • Neoplasm Invasiveness / pathology
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Neoplasms* / etiology
  • Neoplasms* / immunology
  • Neoplasms* / pathology


  • Carcinogens
  • Interleukin-1
  • Methylcholanthrene