In conclusion, this study shows for the first time, to our knowledge, that PDE4 activity is increased in lupus conditions and that among the different PDE4 inhibitors tested, NCS 613, a highly selective PDE4C inhibitor, significantly prevents disease progression by decreasing proteinuria, lowering ex vivo TNFα secretion by PBLs and increasing animal survival rate. This evidence concerns the gene PDE4C and systemic lupus erythematosus.