Subsequent studies demonstrated that the increase in neutrophil S100A8/S100A9 release in diabetic mice also causes reticulated thrombocytosis by activating RAGE on hepatic Kupffer cells, resulting in increased interleukin-6 (IL-6) production and, through increased thrombopoietin production, thrombocytosis (57). This evidence concerns the gene S100A8 and thrombocytosis disease.