MYELOSUPPRESSION IN THE PIG (SUS SCROFA) - UTEROFERRIN REDUCES THE MYELOSUPPRESSIVE EFFECTS OF 5-FLUOROURACIL IN YOUNG-PIGS

The present study investigated the ability of uteroferrin to modulate the myelosuppressive effects of 5-fluorouracil (5-FU) in young pigs (S us scrofa). Pigs (28-35 days of age; n = 6 per treatment) were infused with equal amounts of 5-FU on days 0 and 1 of the experimental period (37.5 mg/kg cumulative dose). Uteroferrin (100 mu g/kg in 0.9% NaCl) or control (equivalent volume of 0.9% NaCl) was administered to pigs a s intramuscular injections twice daily (08:00 and 20:00 hr) on days 1 through 21. Peripheral blood cell number, composition and progenitor c ells were determined over 28 days. Treatment of pigs with 5-FU resulte d in a rapid dose-dependent (P < 0.05) leukocytopenia. Concurrent trea tment of pigs with uteroferrin reduced (P < 0.05) the rate of 5-FU-ind uced leukocytopenia (44 vs 77 +/- 7% decline from baseline on day 3) a nd enhanced (P < 0.05) the recovery from 5-FU on days 10 and 12 postin fusion. The positive effect of uteroferrin on leukocytes resulted prim arily from a protection and/or enhanced recovery of neutrophils and mo nocytes. In addition, uteroferrin attenuated (P < 0.05) the suppressio n of red blood cell numbers after 5-FU administration (6.9 vs 6.1 +/- 0.2 x 10(6) cells/mu l on day 3), an affect reflected in increased hem atocrit and hemoglobin concentrations. The effects of uteroferrin appe ared to result from enhancement of the proliferation and/or differenti ation of primitive pluripotent stem cells resistant to 5 FU, as concur rent treatment of pigs with uteroferrin resulted in a protection and/o r enhanced recovery (P < 0.05) of CFU-GEMM, CFU-GM and BFU-E progenito r cells in the peripheral blood. These results are the first to demons trate that uteroferrin can reduce the myelosuppressive effects of 5-FU in the pig and suggest that uteroferrin has hematopoietic growth fact or activity in vivo. Copyright (C) 1997 Elsevier Science Inc.