Interleukin-1 Beta—A Friend or Foe in Malignancies?

• Main Authors: Rebekka Bent, Lorna Moll, Stephan Grabbe, Matthias Bros
• Format: Article
• Language: English
• Published: MDPI AG 2018-07-01
• Series: International Journal of Molecular Sciences
• Subjects: interleukin-1β; promoter; inflammasome; tumor; tumor-associated macrophage; myeloid-derived suppressor cell
• Online Access: http://www.mdpi.com/1422-0067/19/8/2155

Interleukin-1 beta (IL-1β) is induced by inflammatory signals in a broad number of immune cell types. IL-1β (and IL-18) are the only cytokines which are processed by caspase-1 after inflammasome-mediated activation. This review aims to summarize current knowledge about parameters of regulation of IL-1β expression and its multi-facetted role in pathophysiological conditions. IL-1 signaling activates innate immune cells including antigen presenting cells, and drives polarization of CD4+ T cells towards T helper type (Th) 1 and Th17 cells. Therefore, IL-1β has been attributed a largely beneficial role in resolving acute inflammations, and by initiating adaptive anti-tumor responses. However, IL-1β generated in the course of chronic inflammation supports tumor development. Furthermore, IL-1β generated within the tumor microenvironment predominantly by tumor-infiltrating macrophages promotes tumor growth and metastasis via different mechanisms. These include the expression of IL-1 targets which promote neoangiogenesis and of soluble mediators in cancer-associated fibroblasts that evoke antiapoptotic signaling in tumor cells. Moreover, IL-1 promotes the propagation of myeloid-derived suppressor cells. Using genetic mouse models as well as agents for pharmacological inhibition of IL-1 signaling therapeutically applied for treatment of IL-1 associated autoimmune diseases indicate that IL-1β is a driver of tumor induction and development.