Endogenous steroids are responsible for lactoferrin-induced myelopoiesis in mice

Our previous study revealed that lactoferrin (LF) significantly increases mobilization of the myelocytic lineage in mice. The aim of our current investigation was to determine whether activation of the hypothalamic-pituitary-adrenal axis contributes to this phenomenon. We found that intravenous (iv) injection of LF (10 mg) caused a 48.8% increase in the circulating blood leukocyte count and increased the proportion of the myelocytic lineage (band forms, 10-fold and neutrophils, 2-fold) 24 h post injection. The content of the myelocytic lineage (myelocytes, metamyelocytes, bands and neutrophils) in bone marrow rose from 51.6 to 63.4%. In addition, administration of LF led to a decrease in total thymocyte number by 41.6%. Analogous changes in cell types and numbers in adrenalectomized mice following LF injection were minor. Mifepristone, a blocker of steroid receptors, reversed the effects of LF on leukocyte cell number and bone marrow cell composition. Finally, we showed that LF induced a rise in the serum levels of corticosterone in control but not adrenalectomized mice. We conclude that LF-induced upregulation of endogenous steroid levels is responsible for the stimulation of myelopoiesis.