Effect of interleukin-11 with and without granulocyte colony-stimulating factor on in vivo neonatal rat hematopoiesis: induction of neonatal thrombocytosis by interleukin-11 and synergistic enhancement of neutrophilia by interleukin-11 + granulocyte colony-stimulating factor.
IL-11, a new hematopoietic cytokine isolated from primate stromal cells (PU-34), has been shown to act synergistically with IL-3 to induce proliferation of early hematopoietic stem cells and induce in vitro CFU-MEG proliferation. We hypothesize that recombinant human (rh)IL-11 alone or in combination with granulocyte colony-stimulating factor (G-CSF) might modulate newborn in vivo granulopoiesis and thrombopoiesis. Newborn Sprague-Dawley rats were given 14 d of intraperitoneal rhIL-11 (0-250 micrograms/kg x 14 d), rhIL-11 (250 micrograms/kg) + rhG-CSF (5 micrograms/kg simultaneously x 14 d), rhIL-11 x 7 d followed by G-CSF x 7 d, G-CSF x 14 d, PBS/human serum albumin x 7 d followed by G-CSF x 7 d, or PBS/human serum albumin x 14 d. rhIL-11 alone had no effect on the circulating hematocrit or absolute neutrophil count. There was, however, a significant increase in the circulating platelet count after rhIL-11 (100 and 250 micrograms/kg) versus PBS/human serum albumin (d 13: 1241 +/- 54, 1262 +/- 58 versus 939 +/- 38 k/mm3; p = 0.01). Sequential and simultaneous IL-11 + G-CSF caused a significant increase in the marrow neutrophil reserve and the circulating absolute neutrophil count above that observed when G-CSF alone was administered. IL-11 +/- G-CSF, however, failed to reduce the 96-h mortality rate during experimental group B streptococcal sepsis. These data suggest that IL-11 alone results in a significant elevation in the blood platelet concentration and, in combination with G-CSF, induces an increase in in vivo neonatal rat myelopoiesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Cairo
M S
MS
Genetics Institute, Cambridge, Massachusetts 02140.
Plunkett
J M
JM
Nguyen
A
A
Schendel
P
P
van de Ven
C
C
D000818:Animals; D000831:Animals, Newborn; D004357:Drug Synergism; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006410:Hematopoiesis / Q000187:drug effects*; D017370:Interleukin-11 / Q000008:administration & dosage*; D007964:Leukocytosis / Q000139:chemically induced; D009504:Neutrophils / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013922:Thrombocytosis / Q000139:chemically induced
D017370:Interleukin-11; D016179:Granulocyte Colony-Stimulating Factor