Sequential administration of interleukin-6 and granulocyte-colony stimulating factor in newborn rats: modulation of newborn granulopoiesis and thrombopoiesis.
During states of increased demand, neonatal host defense is characterized by dysregulation of granulopoiesis, resulting in a high incidence of neutropenia. This study investigated the modulation of neonatal rat hematopoiesis by 14-d administration of recombinant human (rh) IL-6, rh-granulocyte-colony stimulating factor (G-CSF), or sequential combination of rhIL-6 and rhG-CSF. Specifically, newborn Sprague-Dawley rats were treated with either rhIL-6 (5 micrograms/kg/d for 14 d), rhG-CSF (5 micrograms/kg/d for 14 d), rhIL-6 for 7 d followed by rhG-CSF for 7 d, PBS/BSA for 7 d followed by rhG-CSF for 7 d, or PBS/BSA for 14 d. RhIL-6 alone significantly increased the peripheral platelet count during the latter part of the 2nd wk of administration (d 13: 980 +/- 42 versus 716 +/- 23 x 10(3)/mm3) (p = less than 0.001) (mean +/- SEM). Treatment with rhIL-6 for 7 d followed by rhG-CSF significantly increased the peripheral neutrophil count compared with 7 d of PBS/BSA and 7 d of G-CSF (d 14 absolute neutrophil count 4888 +/- 12 versus 2720 +/- 317/mm3) (p = less than 0.05). Similarly, sequential rhIL-6/rhG-CSF significantly increased the d-14 bone marrow neutrophil storage pool (9873 +/- 882 versus 3564 +/- 159/mm3) (p = less than 0.005). Lastly, sequential rhIL-6/rhG-CSF induced the highest increase in bone marrow (p less than 0.01) and liver/spleen CFU-GM pool (p less than 0.001) compared with any other treatment group. These studies suggest that rhIL-6 alone is associated with a significant increase in the neonatal platelet count.(ABSTRACT TRUNCATED AT 250 WORDS)
Cairo
M S
MS
Division of Hematology/Oncology, Children's Hospital of Orange County, California 92668.
Plunkett
J M
JM
Nguyen
A
A
Clark
S
S
van de Ven
C
C
D000818:Animals; D000831:Animals, Newborn; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects; D003114:Colony-Forming Units Assay; D004334:Drug Administration Schedule; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects; D006410:Hematopoiesis / Q000187:drug effects*; D015850:Interleukin-6 / Q000008:administration & dosage*; D009503:Neutropenia / Q000188:drug therapy; D051381:Rats; D011919:Rats, Inbred Strains; D013921:Thrombocytopenia / Q000188:drug therapy
D015850:Interleukin-6; D016179:Granulocyte Colony-Stimulating Factor