scholarly journals Macrophage colony-stimulating factor increases hepatic macrophage content, liver growth, and lipid accumulation in neonatal rats

2018 ◽  
Vol 314 (3) ◽  
pp. G388-G398 ◽  
Author(s):  
Clare Pridans ◽  
Kristin A. Sauter ◽  
Katharine M. Irvine ◽  
Gemma M. Davis ◽  
Lucas Lefevre ◽  
...  

Signaling via the colony-stimulating factor 1 receptor (CSF1R) controls the survival, differentiation, and proliferation of macrophages. Mutations in CSF1 or CSF1R in mice and rats have pleiotropic effects on postnatal somatic growth. We tested the possible application of pig CSF1-Fc fusion protein as a therapy for low birth weight (LBW) at term, using a model based on maternal dexamethasone treatment in rats. Neonatal CSF1-Fc treatment did not alter somatic growth and did not increase the blood monocyte count. Instead, there was a substantial increase in the size of liver in both control and LBW rats, and the treatment greatly exacerbated lipid droplet accumulation seen in the dexamethasone LBW model. These effects were reversed upon cessation of treatment. Transcriptional profiling of the livers supported histochemical evidence of a large increase in macrophages with a resident Kupffer cell phenotype and revealed increased expression of many genes implicated in lipid droplet formation. There was no further increase in hepatocyte proliferation over the already high rates in neonatal liver. In conclusion, treatment of neonatal rats with CSF1-Fc caused an increase in liver size and hepatic lipid accumulation, due to Kupffer cell expansion and/or activation rather than hepatocyte proliferation. Increased liver macrophage numbers and expression of endocytic receptors could mitigate defective clearance functions in neonates.NEW & NOTEWORTHY This study is based on extensive studies in mice and pigs of the role of CSF1/CSF1R in macrophage development and postnatal growth. We extended the study to neonatal rats as a possible therapy for low birth weight. Unlike our previous studies in mice and pigs, there was no increase in hepatocyte proliferation and no increase in monocyte numbers. Instead, neonatal rats treated with CSF1 displayed reversible hepatic steatosis and Kupffer cell expansion.

PEDIATRICS ◽  
1968 ◽  
Vol 41 (2) ◽  
pp. 483-494
Author(s):  
Leonard J. Graziani ◽  
Elliot D. Weitzman ◽  
Mutya S. A. Velasco

The maturation of the nervous system of two groups of infants of low birth weight was estimated by the results of a standardized clinical neurologic examination and by evaluation of the electroencephalographic responses to auditory stimuli (clicks). Algebraically summed responses to clicks were recorded simultaneously from 10 scalp electrodes, using a standard electroencephalograph, tape recorder, and a computer of average transients. The results obtained by the two methods were compared with the age postconception, estimated from the maternal history. One group consisted of infants whose birth weights were below the 10th percentile for their gestational age (37.1 ± 2.0 weeks); the other group consisted of infants whose birth weights were similar to the first group but were between the 25th and 75th percentile for their gestational age (31.0 ± 2.3 weeks). In the small-for-age infants, the electroencephalographic responses and the neurologic reflexes were more mature than in the infants of similar birth weights who were not small for age. The results of both examination methods correlated well with the estimated postconception age but less well with birth weight, postnatal age, or somatic growth.


2018 ◽  
Vol 66 (4) ◽  
pp. 245-253
Author(s):  
R. Mbusa-Kambale ◽  
M. Mihigo-Akonkwa ◽  
N. Francisca-Isia ◽  
S. Zigabe-Mushamuka ◽  
J. Bwija-Kasengi ◽  
...  

Blood ◽  
1990 ◽  
Vol 76 (9) ◽  
pp. 1788-1794
Author(s):  
MS Cairo ◽  
JM Plunkett ◽  
D Mauss ◽  
C Van de ven

Single-pulse administration of rhG-colony-stimulating factor (CSF) to neonatal rats was previously demonstrated to induce peripheral neutrophilia and modulate bone marrow (BM) neutrophil storage and proliferative pools (NSP + NPP). In this study, we investigated the prolonged effects of 7 days of rhG-CSF therapy (5 micrograms/kg/per day). Sprague-Dawley newborn rats (less than or equal to 24 hours) were injected intraperitoneally (IP) (daily for 7 days) with rhG-CSF or phosphate-buffered saline/human serum albumin (PBS/HSA). RhG-CSF induced a significant early and late peripheral neutrophilia: 6,905 +/- 1,625 (day 1) and 9,223 +/- 515 microL (day 7) v 1,275 +/- 90/microL (P less than or equal to .0001). In addition, 7 days of rhG-CSF resulted in a significant increase in the BM NSP: 3,247 +/- 190/microL v 1,677 +/- 339/microL (P less than or equal to .001). There was, however, no depletion or significant change in the BM NPP. Seven days of rhG-CSF also induced a mild increase in BM CFU-GM colony formation (P less than or equal to .01). There was, however, no significant change in liver/spleen CFU-GM colonies or in the CFU-GM proliferative rate in either the BM or liver/spleen cultures. Finally, 7 days of prophylactic rhG-CSF therapy resulted in a synergistic response with antibiotic therapy and significantly modulated the mortality rate during experimental group B streptococcal sepsis (GBS) (100% v 50%) (GvsC) (P less than or equal to .001). Pulse rhG-CSF administered at 6 hours or 18 hours after GBS inoculation, however, failed to act synergistically with antibiotics to improve survival or prevent peripheral neutropenia. This study suggests that 7 days of prophylactic rhG-CSF therapy induces peripheral neutrophilia, myeloid maturation, increases neutrophil BM reserves and also may provide immunologic enhancement of neonatal host defense during experimental GBS in term neonatal rats.


Author(s):  
Tuba Ozdemir ◽  
Abdullah Baris Akcan ◽  
Munevver Kaynak Turkmen

<p>OBJECTIVE: In the present study, we investigate the growth characteristics of very low birth weight premature infants of up to two years corrected age, considering the factors affecting growth and catch-up growth time.</p><p>STUDY DESIGN: The demographic data, clinical features, and comorbidities of 77 preterm infants with birth weights of less than or equal to 1.500 g were examined, the infants’ growth statuses in the 40th gestational week (gw) and at 6, 12, 18 and 24 months the corrected age, including their weight, height and head circumference, were evaluated.</p><p>RESULTS: The findings revealed that very low birth weight infants should be closely monitored either during their stay in the Neonatal Intensive Care Unit, or for up to 6 months corrected age, paying particular attention to growth data, and the appropriate supportive treatment should be administered. The applied support process is influential on the future somatic growth of preterm infants. It was noted in the study that bronchopulmonary dysplasia, proven sepsis, respiratory distress syndrome, steroid treatment for more than three days, patent ductus arteriosus, and ibuprofen treatment seemed to affect somatic growth negatively.</p><p>CONCLUSION: Small for gestational age newborns were found to catch up with appropriate for gestational age newborns at 2 years corrected age in terms of growth, although the percentage of catch-up growth during follow-up at the 40thgw, and at the 6th, 12th and 18th months was lower than that of appropriate for gestational age newborns.</p>


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