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

Interleukin-12 (IL-12), a heterodimeric cytokine with potent biological act ivity, was evaluated for effects on proliferation of human immature progeni tor cells in vitro. In vitro proliferation of 5-FU-resistant CD34(+) (G0) p eripheral blood stem cells (PBSC) in response to sequential cytokine stimul ation was examined in the presence and absence of 100 ng/ml IL-12. PBSC wer e found to include a subpopulation of cells that were resistant to 25 mu g/ ml 5-FU and required a combination of IL-12, IL-6 and SCF for the productio n of morphologically recognizable clonogenic elements at day 14 in semisoli d medium. Furthermore, addition of IL-6 soluble receptor (IL-6Rs) to IL-6 a nd SCF led to a similar recruitment, We also demonstrated a significant pro duction of IL-6Rs by CD34(+) cells stimulated by IL-12. We noted that gluco corticoids and aldosterone, a mineralocorticoid, had a positive effect on r ecruitment, but neither mineralocorticoid nor glucocorticoids induced IL-6R s production by CD34(+) cells. The recruitment mechanism by steroids seemed to be different from that used by IL-12. These results confirm previous fi ndings which showed the involvement of IL-12 on immature PBSCs and suggest that IL-12 might pray a key role in early haemopoiesis.