Inhibition of RIPK1 by either genetic or pharmacological means in animal models is highly effective in blocking TNF-induced sepsis, including attenuation of hypothermia and complete rescue of lethality.65,66 Multiple RIPK1 inhibitors have been advanced beyond Phase I safety studies in human clinical trials for the treatment of human inflammatory and neurodegenerative diseases, including rheumatoid arthritis, psoriasis, inflammatory bowel disease, Alzheimer’s disease and amyotrophic lateral sclerosis.14 Here, TNF is linked to rheumatoid arthritis.