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 recombina nt bovine granulocyte-monocyte/macrophage colony stimulating factor (r bGM-CSF) on hematopoiesis in young female pigs. Uteroferrin (100 mu g/ kg in 0.9% NaCl), rbGM-CSF (10 mu g/kg in 0.9% NaCl), uteroferrin + rb GM-CSF (as above), or control (0.9% NaCl) were administered as intramu scular injections twice daily (0800 and 2000 hr). Peripheral blood cel l number, composition, and progenitor cells were determined over 28 da ys. Uteroferrin had minimal effects on white blood cell (WBC) number, while rbGM-CSF caused both a rapid (days 2-7; maximum 122 +/- 8% of ba seline) and late (days 16-28; maximum 133 +/- 8% of baseline) increase in WBC. Combination treatment with uteroferrin + rbGM-CSF abolished t he initial increase in WBC number, but resulted in a prolonged increas e 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 mo nocytes and neutrophils. The addition of uteroferrin + rbGM-CSF enhanc ed (P < 0.05) the initial increase in the monocyte population and augm ented the neutrophilia. In addition, uteroferrin + rbGM-CSF resulted i n a dramatic eosinophilia (days 2-28), which was not detected in eithe r the uteroferrin or rbGM-CSF treatments. Although not substantially a ffected by uteroferrin alone, rbGM-CSF caused an increase (P < 0.05) i n thrombocyte numbers from days 1 through 9 (maximum 133 +/- 11% of ba seline), an effect augmented by cotreatment with uteroferrin. The abil ity of these cytokines to modulate blood cell number and composition a ppeared to result from their effects on hematopoietic progenitor cells . Treatment of pigs with uteroferrin increased (P < 0.05) CFU-GEMM, CF U-GM, and BFU-E progenitor cells in peripheral blood, while rbGM-CSF c aused increases (P < 0.05) relative to control in CFU-GM and CFU-GEMM. These effects were additive, as uteroferrin + GM-CSF augmented the in creases in CFU-GM, BFU-E, and CFU-GEMM. Collectively, these results in dicate that uteroferrin and rbGM-CSF can modulate hematopoiesis in you ng pigs. These effects were both additive and, in the case of neutroph ils and eosinophils, synergistic. Hence, the mechanism(s) by which ute roferrin and rbGM-CSF modulate hematopoiesis appear to be different. ( C) 1997 Elsevier Science Inc.