Cytokines are the best recognized mediators able to induce and orchestrate the many different aspects underlying immune responses. In our investigation we reported that MV release is stimulated by numerous cytokines related to inflammation: IFN-γ and IL-4, studied in more detail, and also IL-13, IL-27, IL-23, and TGF-β. The unexpected result was the very similar effect on MV release induced by the first two cytokines, which induce opposite effect in inflammation: stimulation by IFN-γ and inhibition by IL-4. Therefore, the stimulation of MV release might be not a direct consequence to inflammation per se, since it is also involved in the mechanisms acting in its resolution. Enhanced MV production in response to pro-regenerative or inflammatory cytokines may rather reflect the increased capacity of reactive microglia to communicate with the microenviroment. This is in line with the fact that, by intricate feedback loops, pro- and anti-inflammatory cytokines regulate their own expression as well as the activity of the antagonist cytokines balancing and stabilizing inflammatory reactions (43). During chronic inflammation, such as that occurring in neurological disorders like multiple sclerosis, it is likely that the two types of cytokines play coordinated effects.