Anemic stress promotes an emergency production of red blood cells. It is best understood in mice where it occurs in the spleen. However, emergency red blood cell production in both human and mouse utilize signals and precursor cells that are different from regular red blood cell production. These precursor cells are capable of self-renewal but they are restricted to become red blood cells. Inflammation and anemic stress promotes the production of these precursor cells but they do not turn into red blood cells until a specific serum level increases. This specific serum promotes the transition of these precursor cells into red blood cells by acting on the macrophages in the spleen. During the production of precursor cells, macrophages produce protein that promote the production of precursor cells but inhibits them to form into red blood cells. When this specific serum is on high level, it changes the biosynthesis in the macrophages to stop producing the protein, thus promoting the formation of red blood cells from the precursor cells.