IL-17 STIMULATES GRANULOPOIESIS IN MICE - USE OF AN ALTERNATE, NOVEL GENE THERAPY-DERIVED METHOD FOR IN-VIVO EVALUATION OF CYTOKINES

IL-17 is a novel cytokine secreted principally by CD4(+) T cells. It h as been shown to support the growth of hemopoietic progenitors in vitr o; however, its in vivo effects are presently unknown. Adenovirus-medi ated gene transfer of the murine IL-17 cDNA targeted to the liver (5 x 10(9) plaque-forming units (PFU) intravenous) resulted in a transient ly transgenic phenotype, with dramatic effects on in vivo granulopoies is. Initially, there was a significant increase (fivefold) in the peri pheral white blood count (WBC), including a 10-fold rise in the absolu te neutrophil count. This was associated with a doubling in the spleen size over 7-14 days after gene transfer, which returned to near basel ine by day 21, although the white blood cell count remained elevated. There was a profound stimulation of splenic hemopoiesis as demonstrate d by an increase in total cellularity by 50% 7 days after gene transfe r and an increase in hemopoietic colony formation. A maximal increase in frequency of high proliferative potential colonies (HPPC) (11-fold) and CFU-granulocyte-macrophage (GM) and CFU-granulocyte-erythrocyte-m egakaryocyte-monocyte (GEMM) (CFU) (6-fold) was seen on day 3 after IL -17 gene transfer. Both CFU and HPPC remained significantly elevated i n the spleen throughout day 21, but at reduced levels compared with da y 3, Bone marrow CFU and HPPC were elevated on day 3 only by 75% and 2 5%, respectively, without changes in total cellularity, Thus, murine I L-17 is a cytokine that can stimulate granulopoiesis in vivo. Since IL -17 is principally produced by CD4(+) T cells, this cytokine could hav e therapeutic implications in AIDS-related bone marrow failure and opp ortunistic infections.