title: Erythroid progenitors in polycythemia vera demonstrate a different response pattern to IL-4 compared to the normal BFU-E from peripheral blood.
abstract: Human recombinant interleukin 4 (IL-4) was studied for its effects on erythroid burst-forming units (BFU-E) from normal peripheral blood and from patients with polycythemia vera (PV). IL-4 enhanced the proliferation of normal peripheral blood BFU-E (183% +/- 20% enhancement), whereas in the presence of interleukin 3 (IL-3) no further augmentation was noticed. The IL-4-mediated effects were independent of the absence or presence of adherent cells, B cells, or T cells. These data are in contrast with results obtained from normal human bone marrow cells, in which IL-4 antagonized the enhancing effects of IL-3. In PV a different response pattern was observed. The effects of IL-4 on the erythropoietin (Epo)-independent BFU-E were variable. In five PV patients no suppressive or enhancing effects of IL-4 were observed, whereas in two additional patients a significant decline in the Epo-independent BFU-E was noted. In the presence of IL-3, IL-4 significantly antagonized the IL-3-supported Epo-independent BFU-E in all patients (272% +/- 57% vs 187% +/- 49% enhancement, p less than 0.05). In contrast, IL-4 did not modify the IL-3-supported Epo-dependent BFU-E. In summary, these data suggest a difference between the normal and PV peripheral blood BFU-E. The Epo-dependent erythroid progenitors in PV patients showed a response pattern with IL-3 and IL-4 comparable to that of normal peripheral blood BFU-E, whereas the Epo-independent erythroid progenitors behaved like normal human bone marrow BFU-E, suggesting a shift in the stem cell compartment in PV. This is further supported by the finding that erythroid colony-forming units (CFU-E), normally only present in the bone marrow, could be cultured from the peripheral blood of PV patients in the presence or absence of Epo.
authors.affiliation: Department of Medicine, University of Groningen, The Netherlands.
authors.forename: J T
authors.initials: JT
authors.lastname: de Wolf
authors.forename: D W
authors.initials: DW
authors.lastname: Hendriks
authors.forename: J A
authors.initials: JA
authors.lastname: Beentjes
authors.forename: M T
authors.initials: MT
authors.lastname: Esselink
authors.forename: J W
authors.initials: JW
authors.lastname: Smit
authors.forename: M R
authors.initials: MR
authors.lastname: Halie
authors.forename: E
authors.initials: E
authors.lastname: Vellenga
mesh_terms: D001402:B-Lymphocytes / Q000502:physiology; D004347:Drug Interactions; D015672:Erythroid Precursor Cells / Q000187:drug effects*; D004921:Erythropoietin / Q000494:pharmacology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D011087:Polycythemia Vera / Q000097:blood*; D013601:T-Lymphocytes / Q000502:physiology
chemical_list: D007377:Interleukin-3; D004921:Erythropoietin; D015847:Interleukin-4