Because it has beenreported that TNF-α transgenic micedevelop arthritis with enhanced productionof TNF-α, IL-1, and IL-6[29], whichmeans TNF-α is the major dominant regulator of IL-1βand IL-6 [30].Additional explanation of antipannus forming effects of PDE4inhibitors is the inhibition offibroblast proliferation. This evidence concerns the gene TNF and Arthritis.