Abstract
Research in our unit has focused on several aspects of acute inflammatory shock induced by pro-inflammatory molecules, such as the cytokines TNF and IL-1, and the bacterial cell wall component, LPS. We have paid special attention to the study of TNF in mouse models for two reasons. First, TNF has a very potent anti-tumor effect, especially when combined with IFN-gamma (IFNγ), melphalan, or other chemotherapeutics. This anti-tumor activity is directed to the neovasculature of the tumor [1] and so it is applicable to all solid tumors regardless of their location, tissue type, or degree of progression. Second, TNF exerts very powerful pro-inflammatory effects. Indeed, administration of TNF to healthy volunteers, cancer patients, or experimental animals leads to systemic inflammation so serious that lethal shock can occur [2]. Chronically dysregulated TNF expression is also an essential step in the development of several diseases that impose a heavy social and economic burden, such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and asthma [3]. The major aim of most of the unit’s research has been the acquisition of novel insights into the endogenous mechanisms of protection against serious inflammation and their possible application to ameliorating the inflammation induced by TNF in disease and the potential development of TNF-based anti-cancer therapy. In this chapter we will discuss the three different approaches we have been using to discover relevant protective genes and molecules.
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Van Hauwermeiren, F. et al. (2011). Strategies to Inhibit the Toxicity of Systemic TNF Treatment. In: Wallach, D., Kovalenko, A., Feldmann, M. (eds) Advances in TNF Family Research. Advances in Experimental Medicine and Biology, vol 691. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6612-4_49
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DOI: https://doi.org/10.1007/978-1-4419-6612-4_49
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