In that case, cytokines most commonly do not directly affect the target cells but interact with other biologically active factors to achieve the effect of immunosuppression. There are some papers describing fine differences in MSC secreted cytokine profiles with immunoregulatory effects but in this PARP Inhibition review the generally accepted cytokines most often cited in the literature are discussed. The mechanisms of immunomodulation

by direct cellular contacts will not be discussed in this review. MSCs isolated from different tissues are different in some fine specifics as mentioned above. However, no data have been published describing significant differences in the profiles of secreted cytokines by different types of MSCs. Most authors report either a lack of differences or find some quantitative differences in the levels of cytokines secreted by AT-MSCs or BM-MSCs[58-60]. Our experimental data also show some quantitative differences in the cytokine secretion[37]. Similar findings are reported when embryonic, fetal and adult MSCs have been compared[61]. MSCs secrete cytokines either “spontaneously” or after induction by other cytokines, the most important being IFNγ, TNFα and IL-1β[62-64],

and it should be underlined that MSCs are not always immunosuppressive. It is assumed that their effects are determined by the local conditions of the microenvironment and sometimes the pro-inflammatory IFNγ, TNFα and IL-1β cytokines

may induce secretion of anti-inflammatory immunosuppressive factors. Engagement of certain Toll-like receptors (TLR) expressed by MSCs can determine their pro or anti-inflammatory effects[65-67]. The definition of cytokines as pro or anti-inflammatory is quite far from their real effects because it seems that there is not a single cytokine which is not engaged in both types of reactions. Nevertheless, that definition is quite convenient and will be used further in the present review. The most important immunoregulatory cytokines described in the literature are presented in Table ​Table11. Table 1 Cytokines secreted by mesenchymal stem cells and the corresponding target cells INTERLEUKIN 10 Interleukin AV-951 10 (IL-10) is pleiotropic cytokine identified in the 1980s and characterized by its anti-inflammatory effect related to the induction of immune tolerance[68-71]. It has been established that IL-10 suppresses the functions of macrophages and neutrophils[70,72], inhibits the Th1 immune response[70,73-76], influences NF-kB synthesis[77] and causes expression of anti-inflammatory molecules, such as protease inhibitors[78] and IL-1 and TNFα antagonists[79]. The major function of IL-10 in induction of immune tolerance is its effect on the antigen presenting cells and particularly on the dendritic cells (DCs).