The effect of uteroferrin and recombinant GM-CSF on hematopoietic parameters in normal female pigs (Sus scrofa)

The present study investigated the effect of uteroferrin and recombinant bovine granulocyte-monocyte/macrophage colony stimulating factor (rbGM-CSF) on hematopoiesis in young female pigs. Uteroferrin (100 micrograms/kg in 0.9% NaCl), rbGM-CSF (10 micrograms/kg in 0.9% NaCl), uteroferrin + rbGM-CSF (as above), or control (0.9% NaCl) were administered as intramuscular injections twice daily (0800 and 2000 hr). Peripheral blood cell number, composition, and progenitor cells were determined over 28 days. Uteroferrin had minimal effects on white blood cell (WBC) number, while rbGM-CSF caused both a rapid (days 2-7; maximum 122 +/- 8% of baseline) and late (days 16-28; maximum 133 +/- 8% of baseline) increase in WBC. Combination treatment with uteroferrin + rbGM-CSF abolished the initial increase in WBC number,but resulted in a prolonged increase in WBC number (days 14-28) relative to control. The rbGM-CSF-induced increase in WBC number resulted from rapid increases (P < 0.05) in monocytes and neutrophils. The addition of uteroferrin + rbGM-CSF enhanced (P < 0.05) the initial increase in the monocyte population and augmented the neutrophilia. In addition, uteroferrin + rbGM-CSF resulted in a dramatic eosinophilia (days 2-28), which was not detected in either the uteroferrin or rbGM-CSF treatments. Although not substantially affected by uteroferrin alone, rbGM-CSF caused an increase (P < 0.05) in thrombocyte numbers from days 1 through 9 (maximum 133 +/- 11% of baseline), an effect augmented by cotreatment with uteroferrin. The ability of these cytokines to modulate blood cell number and composition appeared to result from their effects on hematopoietic progenitor cells. Treatment of pigs with uteroferrin increased (P < 0.05) CFU-GEMM, CFU-GM, and BFU-E progenitor cells in peripheral blood, while rbGM-CSF caused increases (P < 0.05) relative to control in CFU-GM and CFU-GEMM. These effects were additive, as uteroferrin + GM-CSF augmented the increases in CFU-GM, BFU-E, and CFU-GEMM. Collectively, these results indicate that uteroferrin and rbGM-CSF can modulate hematopoiesis in young pigs. These effects were both additive and, in the case of neutrophils and eosinophils, synergistic. Hence, the mechanism(s) by which uteroferrin and rbGM-CSF modulate hematopoiesis appear to be different.