Evaluation of proinflammatory and immunosuppressive cytokines in blood and bone marrow of healthy hematopoietic stem cell donors

Immunological Heterogeneity of Healthy Peripheral Blood Stem Cell Donors—Effects of Granulocyte Colony-Stimulating Factor on Inflammatory Responses

“…Previous studies suggest that healthy stem cell donors are heterogeneous with regard to the effects of G-CSF on donor immunoregulation and the number, as well as the functional status, of immunocompetent graft cells [ 9 , 13 , 15 , 18 , 19 , 20 , 21 ]. One of these studies even suggests that G-CSF induced donor heterogeneity is important for outcome after allotransplantation [ 21 ].…”

“…We have previously reviewed and discussed the available evidence for a role of IL-6 in the development of immune-mediated complications after allotransplantation [ 27 ]. Previous studies have also shown that systemic IL-6 levels in healthy stem cell donors can be altered by G-CSF therapy; these effects are divergent, and although increased levels are seen for most donors, a minority of them show decreased systemic IL-6 levels in response to G-CSF [ 9 , 19 , 28 ]. In our present study we observed that healthy donors undergoing G-CSF induced stem cell mobilization and harvesting by leukapheresis are heterogeneous, both with regard to the G-CSF induced acute phase reaction and effects of G-CSF on systemic levels of various IL-6 cytokine/receptor family members.…”

“…It can be seen from Figure 3 that the in vitro G-CSF effects on the monocyte release of IL-6 differed between healthy individuals (although increased IL-6 levels were most common). Previous in vivo studies also suggest that the effects of G-CSF on IL-6 vary between individuals, i.e., the effect of G-CSF therapy on systemic IL-6 levels of healthy stem cell donors differs and both increased, unaltered, and decreased systemic levels can be seen [ 9 , 19 ].…”

“…However, several studies have demonstrated that the immunomodulatory effects of G-CSF-induced stem cell mobilization differ between healthy donors [ 18 ]. Firstly, the effects of G-CSF on serum levels of a wide range of both pro- and anti-inflammatory cytokines, as well as soluble adhesion molecules and extracellular proteases, differ between healthy donors [ 9 , 19 ]; Secondly, the effect of G-CSF on immunoregulatory metabolites also varies [ 13 ]; Thirdly, the numbers of different immunocompetent cell subsets vary between grafts derived from different donors [ 20 ]; Finally, a recent study suggests that the responsiveness of immunocompetent cells to G-CSF administration differs between healthy donors, i.e., there are qualitative differences, and not only quantitative differences, between grafts derived from different donors [ 21 ]. An important question is therefore whether the G-CSF induced immunomodulation is heterogeneous and whether such differences between donors have an impact on outcome after allotransplantation [ 16 ].…”

“…This is also supported by previous studies of post-transplant G-CSF therapy in allotransplant recipients; whether G-CSF therapy will influence post-transplant survival depends on the conditioning therapy and the type of stem cell graft [ 26 ]. We have previously reviewed the scientific evidence for a role of IL-6 in the development of immune-mediated complications after allotransplantation [ 27 ], and previous studies have also shown that IL-6 serum levels are altered during G-CSF mobilization for a large subsets of healthy stem cell donors [ 9 , 19 , 28 ]. Even though risk-adapted GVHD prophylaxis based on variations in graft composition is already considered, a better understanding of the mechanisms behind, and the consequences of, donor and graft heterogeneity is needed, including the possible roles of the IL-6 family and the contribution of G-CSF to the heterogeneity.…”