IL-6 has a significant role in the triggering of humoral immune response by stimulating the B cell differentiation and secretion of antibodies[95]. Some recent data demonstrate that IL-6 together with buy BRL-15572 TGFβ is engaged in regulation of the

balance between the pro-inflammatory Th17 and immunosuppressive response mediated by Tregs as both cytokines acting together induce expression of RORγt which is the major transcription factor defining the Th17 cells[94,95]. Recently, simultaneously to the proven pro-inflammatory function of IL-6, quite convincing data have piled up about its function as an anti-inflammatory cytokine. It has been established that IL-6 suppresses the secretion of many pro-inflammatory cytokines, such as IL-1, TNFα, GM-CSF, IFNγ, but on the other hand, it induces the synthesis of glucocorticoids, IL-10, IL-1 receptor antagonist and soluble receptor for ТNFα[72,75,79,96]. It has been demonstrated that IL-6 exerts its anti-inflammatory effect both locally and systemically because mice deficient to IL-6 gene have increased production of pro-inflammatory TNFα, GM-CSF and MIP-2[72]. Moreover, some new results show that IL-6 is a

key factor in the formation and functions of the CD8+FoxP3+ cell population, which is related to suppression of the Th17 immune response[97]. Altogether, these data show that IL-6 has a “two sided” engagement in the modulation of the immune response by regulatory and Th17 cells. On one hand, IL-6 together with TGFβ induces formation of Th17 cells and on the other hand, IL-6 directly inhibits this response by its effect on CD8+FoxP3+ (Figure ​(Figure11). Figure 1 Effect of Interleukin 6 on Th17 formation. IL-6 exerts a dual effect on the generation of Th17 cells. On one side, IL-6 in concert with TGFβ facilitates the generation of this cell population and on the other side, IL-6 inhibits the Th17 cells … Contrary to IL-10, there is no doubt that IL-6

is secreted by MSCs and almost all authors agree with this statement[69,78,82,84,86,87]. Its secretion by MSCs has been demonstrated both in mice and in humans[62,66] and is detected either after induction with TNFα, IL-1b and IFNγ or spontaneously[37,61-63,72,95]. Batimastat When MSCs were tested for 120 cytokines at mRNA and protein levels, it was established that IL-6 has the highest expression and the conclusion was made that IL-6 was the basic cytokine responsible for the immunoregulatory effects of MSCs[60]. After the secretion of IL-6 by MSCs, a suppression of the apoptosis of neutrophils is observed[64,68,81] and this effect could be very important for the connection between defects of apoptosis and triggering of autoimmune reactions. However, it is still not truly clarified whether IL-6 causes generation of classical Treg cells (CD4+FoxP3+), although there is no doubt about its direct effect on the generation of CD8+FoxP3+ cells.