In a rat model of FCA-induced arthritis, the synergistic effect of TMZ and MTX produced the best results by increasing the level of adenosine, which acts through different mechanisms, including inhibition of microvesicular shedding of FADD, eliminating its intracellular anti-inflammatory effect and downregulation of the TLR signaling pathway (Figure 9). Here, FADD is linked to arthritic joint disease.