Interleukin 2 interacts with myeloid growth factors in serum-free long-term bone marrow culture.
IL2 infusion may benefit patients with haematological malignancies by lowering the disease burden. However, conflicting data have been reported on IL2 effects on myelopoiesis, in vitro as well as in vivo. In the present study we investigated the ability of IL2 to act on committed and primitive bone marrow progenitor cells in defined serum-free (SF) culture conditions which avoid many technical biases such as interference by exogenous stimulating or inhibiting factors. Low doses of IL2 (0.1-1000 U/ml) were studied without or in combination with recombinant IL3, GM-CSF and erythropoietin, in SF long-term marrow culture (LTMC). We report data in favour of an inhibitory activity of IL2 limited to committed progenitors and excluding more primitive haemopoietic stem cells, as shown by an alteration of CFU-GM proliferation during the first 5 weeks of LTMC, decreasing with time, unaffected BFU-E and increased nucleated cell production. Beyond week 5, no difference was observed between IL2 supplemented cultures and the SF control cultures. In parallel, IL2 induced the adherence of fibroblastic cells and their progeny. In addition to the inhibitory effect, IL2 appeared to limit the stimulating effect on granulopoiesis and erythropoiesis of myeloid growth factors (GF) such as combination of IL3, GM-CSF and EPO. Indeed, in SF-LTMC conditions, IL2 inhibitory effect is effective on CFU-GM production throughout the 7 weeks of LTMC and on BFU-E during the first 2 weeks only. These data confirm the interaction of IL2 with other GFs in the complex interplay of the cytokine network.
Douay
L
L
Unité de Recherche sur Les Greffes de Cellules Souches Hématopoïétiques, CHU Saint-Antoine, Paris, France.
Giarratana
M C
MC
Mary
J Y
JY
Gorin
N C
NC
D001854:Bone Marrow Cells; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D016895:Culture Media, Serum-Free; D004347:Drug Interactions; D004921:Erythropoietin / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors
D003115:Colony-Stimulating Factors; D016895:Culture Media, Serum-Free; D007376:Interleukin-2; D007377:Interleukin-3; D011994:Recombinant Proteins; D004921:Erythropoietin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor