Schematic of TNF inhibitors and their mode of action. Receptor (i.e. etanercept, lenercept) and antibody based (i.e. infliximab, adalimumab, golimumab) anti-TNF biologics inhibit both solTNF and tmTNF. TNF variants (DN-TNFs) exchange with native solTNF monomers to form heterotrimers with drastically reduced abilities to bind TNF receptors, making them selective for solTNF signaling inhibition. Small molecule inhibitors of TNF signaling include minocycline which decreases TNF synthesis, thalidomide which enhances degradation of TNF mRNA, and TACE inhibitors which prevent TACE induced release of solTNF.