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

Interleukin-1 (IL-1) comprises a family of closely related genes; the two major agonistic proteins, IL-1 alpha and IL-1 beta, are pleiotropic and affect mainly inflammation, immunity and haemopoiesis. IL-1 beta is active solely in its secreted form, whereas IL-1 alpha 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-1 alpha expressed on malignant cells stimulates anti-tumour immunity, while secretable IL-1 beta 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-1 alpha and IL-1 beta in malignant cells or in the tumour's micro-environment may open new possibilities for using IL-1 in cancer immunotherapy. (c) 2006 Elsevier Ltd. All rights reserved.