The previously reported mitogenic properties of IL-4 (24) were not observed in our cell systems. Actually, in agreement with previous observations (21, 23), significant anti-proliferative effects were observed for IFN-γ and, although to a lesser extent, IL-4. With further experiments we revealed that cytokine-induced shedding is fully different from all steps of the ATP/P2X7-R signaling axis: in fact, antagonists of the receptor such as oxATP and BBG did not reduce MV numbers. The involvement of pannexin-1, the hemichannel associated to P2X7, was excluded by probenecid treatment as well as by using a more specific inhibitor, a synthetic blocking peptide.