IL-12 indirectly enhances proliferation of 5-FU-treated human hematopoietic peripheral blood CD34+ cells

Abstract

Interleukin-12 (IL-12) or natural killer cell stimulatory factor (NKSF), has multiple effects on T lymphocytes and natural killer cells. In this study, the effect of IL-12 on human hematopoiesis was studied by analyzing the growth of CD34+ peripheral blood stem cells (PBSC), in steady state. In the presence of Epo, IL-12 alone or in combination with IL-3 or SCF had no effect on the formation of colonies from CD34+ cells. In culture with Epo, G-CSF, and IL-3, the effect of Flt3-ligand (FL) on CD34+ PBSC was investigated in the presence or absence of IL-12. No additional effect of IL-12 was observed when combined with FL. We evaluated 5-FU-treated human CD34+ PBSC proliferation in cultures with Epo, G-CSF, and IL-3, in the presence or absence of IL-12. No cytokine combination enhanced colony formation from 5-FU-treated CD34+ cells. However, in cultures of 5-FU-treated human CD34+ cells, the most efficient combination was IL-3 + Epo + G-CSF + Accessory cells (CD34-). Furthermore, IL-12 enhanced this colony formation significantly. To investigate whether immature CD34+ cells were responsible for FL or SCF, 5-FU-treated human CD34+ cells were cultured with or without IL-12. Whereas no synergistic effect was observed in combination with IL-12, SCF alone significantly enhanced colony formation. However, the colony number was found to be smaller than with the potent combination of accessory cells in the presence of IL-12. These results indicate that accessory cells, lost in CD34+ cell purification, could be partly responsible for an IL-12 effect on immature human PBSC proliferation.

Recruitment of primitive peripheral blood cells: synergism of interleukin 12 with interleukin 6 and stem cell factor

“…Although IL‐12 was originally identified as an activator of natural killer cells and of T lymphocytes (Kobayashi et al , 1989; Wolf et al , 1991; Stern et al , 1990; Gubler et al , 1991), our previous results have clearly demonstrated that this cytokine has the capacity to stimulate proliferation of primitive progenitor cells, in the presence of accessory cells (Grafte et al , 1998). The haemopoietic effects of IL‐12 are generally observed only in combination with other factors (Fardoun‐Joalland et al , 1995).…”

“…The IL‐12 effect on human haemopoiesis remains unclear. This report was aimed at explaining previous results which have shown an IL‐12 effect on immature peripheral blood stem cells (PBSCs), only in the presence of CD34‐negative cells (Grafte et al , 1998). The potential synergism between IL‐12 and others cytokines, especially in early human haemopoiesis, was of particular interest.…”

A Review of Clinical and Preclinical Studies on Therapeutic Strategies Using Interleukin-12 in Cancer Therapy and the Protective Role of Interleukin-12 in Hematological Recovery in Chemoradiotherapy

“…Fardoun-Joalland et al [ 23 ] and Grafte et al [ 24 ] studied the in vitro efficacy of IL-12, using normal human peripheral blood and bone marrow mononuclear cells, respectively. They showed that in combination with rhIL-3, erythropoietin, or G-CSF, rhIL-12 could significantly enhance the formation of cell colonies.…”

Comparison of interleukin-12 with lung cancer and malignant lymphoma undergoing autologous peripheral blood stem cell transplantation

“…Accordingly, PBSCT may enhance engraftment by producing cytokines and accelerating hematopoietic reconstitution, and clinical attention has recently focused on the in vivo secretion of hematopoietic growth factors following high-dose chemotherapy and PBSCT. Furthermore, recent studies have suggested that IL-12 may be involved in dierentiation of early resting hematopoietic progenitor cells, and that IL-12, like other hematopoietic factors, may be an inducer of growth and dierentiation of immature progenitor cells (Jacobsen et al 1993;Ogawa 1993;Fardoun-Joalland et al 1995;Grafte et al 1998;Grafte et al 1999). …”