XPro1595, an engineered dominant-negative TNF that inactivates only solTNF [10], has proven to be effective in animal models of CNS disorders involving increased TNF production [3,11,12], and in attenuating experimental arthritis [13] and endotoxin-induced liver injury [14], without suppressing the innate immunity to infection, in contrast to etanercept treatment. This evidence concerns the gene TNF and arthritic joint disease.