Tumour Necrosis Factor Alpha

Tumour necrosis factor alpha (TNFα) is a cytokine produced by a range of cells (Monteleone et al., 2013). It has two receptor subtypes, and binding to these triggers inflammatory pathways (Monteleone et al., 2013).

In patients with IBD, levels of TNFα are increased systemically as well in the intestine (Holleran et al., 2017). TNFα is one of the main pro-inflammatory cytokines in IBD, with a key role in pathogenesis (Argollo et al., 2017; Pedersen et al., 2014; Neurath, 2014).

Depending on the cytokine environment and receptor subtype, pro-inflammatory effects differ (Video 6) (Kalliolas and Ivashki 2016; Neurath, 2014):

Video 6. Animation outlining the various TNF pathways in IBD (Kalliolas & Ivashki 2016; Neurath, 2014).
IEC: intestinal epithelial cell; MLCK, myosin light chain kinase; NF-κB, nuclear factor kappa B, RIPK, receptor-interacting protein kinase, TIMP1, tissue inhibitor of matrix metalloproteinase 1, TNF receptor-associated factor 2.

TNFα has been the most studied of the pro-inflammatory cytokines in IBD (Pedersen et al., 2014), and blocking this has become one of the standard clinical therapies (Neurath, 2014). However, improved understanding of the basic science may ultimately provide further treatment benefits (Kalliolias & Ivashki, 2016).