The role of cytokines in modulating neonatal myelopoiesis and host defense.
Neonatal sepsis is a major cause of morbidity and mortality in newborn infants. Hematopoiesis and host defense in the neonate is developmentally immature compared with the adult. Defects in both the quantitative and qualitative aspects of the phagocytic system contribute significantly to a relative state of immunodeficiency in the neonate. Dysregulation of neonatal hematopoiesis and the immune response is a significant contributing factor to the increased susceptibility of the neonate to infection. A relatively small set of pluripotent stem cells gives rise to large numbers of functionally diverse mature effector cells. Cell proliferation and differentiation are regulated and controlled by highly specific protein factors, affecting single and multiple lineage hematopoiesis. Reduced neonatal rat myeloid progenitor pools, accelerated myeloid progenitor proliferative rates and decreased total body neutrophil storage pools predispose the newborn rat to depletion of mature effector neutrophils and a tendency to develop neutropenia during states of increased demand such as overwhelming bacterial infection. We review here the multifactorial complex biological process involved in the regulation of hematopoietic growth factors. We also review the biological effects of various non-lineage-committed and lineage-committed growth factors as reported in in vitro investigations and in vivo neonatal animal experiments. We also review our results of phase I/II clinical studies utilizing rhuG-CSF in neonates with presumed sepsis, and of rhuGM-CSF in very low birth weight neonates.
Rosenthal
J
J
Division of Hematology/Oncology, Children's Hospital of Orange County, Orange, CA 92668, USA.
Cairo
M S
MS
D000818:Animals; D000831:Animals, Newborn; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000502:physiology*; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use; D006133:Growth Substances / Q000502:physiology; D006410:Hematopoiesis / Q000276:immunology / Q000502:physiology; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D019891:Leukopoiesis / Q000276:immunology / Q000502:physiology*; D010587:Phagocytosis; D051381:Rats; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use
D016207:Cytokines; D006133:Growth Substances; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor