When K115R mice were challenged by intravenous injection of TNF (500 μg/kg body weight) in a TNF-induced systemic inflammatory response syndrome (SIRS) model, they exhibited a significantly higher morbidity (Mantel–Cox test p = 0.0095) (Fig. 1i) and a more pronounced drop in body temperature than WT littermates (Fig. S2A). Here, TNF is linked to systemic inflammatory response syndrome.