[The effect of specific interleukin-1 receptor blockade on hematopoietic stem cell proliferation]

Interleukin-1 plays a key role in the regulation of hematopoiesis. One of the major controlling mechanisms of IL-1 activites is mediated through IL-1ra. In this report we investigated whether IL-1ra might function as a true negative growth regulator of hematopoietic cells. The effect of rIL-1ra on the proliferation of early- and late-appearing CFU-S was assessed in regenerating bone marrow during the recovery after sublethal damage by X-irradiation. To this, regenerating bone marrow cells of CBA/H mice, obtained 3 days after 2 Gy irradiation, were preincubated 90 min to 5 hr with increasing concentrations of rIL-1ra (5-100 ng/ml). To determine the proliferative activity of CFU-Sd12 and CFU-Sd8, cytosine-arabinoside was added for the last 1 hr of incubation. The results revealed significant dose-dependent inhibition of CFU-Sd12, but not of CFU-Sd8 cycling after IL-1 receptor blackade with rIL-1ra over 10 ng/ml. The data implicate IL-1 receptor involvement in the proliferative activity of hematipoietic stem cells, but suggest that prevention of cell cycling by IL-1ra depends on the position of target cells in the heterogenous stem cell compartment.