TNF and Werner syndrome: Because p38 activation leads to the production of pro-inflammatory cytokines such as IL-1 and TNFα (Ferran et al. 1995), it is possible that elevated p38 activity in vivo in WS individuals may lead to the observed elevated levels of p38-inducible inflammatory cytokines, and thus plays a role in WS pathophysiology (Davis and Kipling 2006).