Title: <i>In vivo</i> effects of interleukin‐17 on haematopoietic cells and cytokine release in normal mice
Abstract: Abstract. In order to gain more insight into mechanisms operating on the haematopoietic activity of the T‐cell‐derived cytokine, interleukin‐17 (IL‐17) and target cells that first respond to its action in vivo , the influence of a single intravenous injection of recombinant mouse IL‐17 on bone marrow progenitors, further morphologically recognizable cells and peripheral blood cells was assessed in normal mice up to 72 h after treatment. Simultaneously, the release of IL‐6, IL‐10, IGF‐I, IFN‐γ and NO by bone marrow cells was determined. Results showed that, in bone marrow, IL‐17 did not affect granulocyte‐macrophage (CFU‐GM) progenitors, but induced a persistant increase in the number of morphologically recognizable proliferative granulocytes (PG) up to 48 h after treatment. The number of immature erythroid (BFU‐E) progenitors was increased at 48 h, while the number of mature erythroid (CFU‐E) progenitors was decreased up to 48 h. In peripheral blood, white blood cells were increased 6 h after treatment, mainly because of the increase in the number of lymphocytes. IL‐17 also increased IL‐6 release and NO production 6 h after administration. Additional in vitro assessment on bone marrow highly enriched Lin − progenitor cells, demonstrated a slightly enhancing effect of IL‐17 on CFU‐GM and no influence on BFU‐E, suggesting the importance of bone marrow accessory cells and secondary induced cytokines for IL‐17 mediated effects on progenitor cells. Taken together, these results demonstrate that in vivo IL‐17 affects both granulocytic and erythroid lineages, with more mature haematopoietic progenitors responding first to its action. The opposite effects exerted on PG and CFU‐E found at the same time indicate that IL‐17, as a component of a regulatory network, is able to intervene in mechanisms that shift haematopoiesis from the erythroid to the granulocytic lineage.