TNF and systemic inflammatory response syndrome: In previous work, we have shown that decreased TNFR1 expression (50% in TNFR1+/− mice) leads to complete resistance to TNF-induced SIRS in a non-linear gene-dosage way, meaning that 2× reduction in TNFR1 protein leads to increased LD50 of > 40× (Van Hauwermeiren et al, 2013) and this is linked with decreased TNF-induced intestinal barrier dysfunction (Van Hauwermeiren et al, 2014).