Cytokine production and function in c-mpl-deficient mice: No physiologic role for interleukin-3 in residual megakaryocyte and platelet production

Abstract

Mice lacking thrombopoietin (TPO), or its receptor c-Mpl, display defective megakaryocyte and platelet development and deficiencies in progenitor cells of multiple hematopoietic lineages. The contribution of alternative cytokines to thrombopoiesis in the absence of TPO signalling was examined in mpl(-/-) mice. Analysis of serum and organ-conditioned media showed no evidence of a compensatory over-production of megakaryocytopoietic cytokines. However, consistent with a potential role in vivo, when injected into mpl(-/-) mice, interleukin-6 (IL-6) and leukemia inhibitory factor (UF) retained the capacity to elevate megakaryocytes and their progenitors in hematopoietic tissues and increase circ..