Insulin-like growth factor-1 replacement therapy after extremely premature birth: An opportunity to optimize lifelong lung health by preserving the natural sequence of lung development

Kramer, Boris W.; Daly, Mandy; Jobe, Alan H.; Niklas, Victoria

doi:10.1016/j.prrv.2023.05.001

Cited by 2 publications

(2 citation statements)

References 55 publications

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“…The authors posited that impaired placental lipid trafficking occurred as a consequence of the etiology causing fetal growth restriction but speculate that this may impact fetal growth. These findings may also raise further concern for preterm neonates given PN lipid, as IGF-1 levels fall and are low following preterm birth [ 67 ].…”

Section: Discussionmentioning

confidence: 99%

Physiological response to fetal intravenous lipid emulsion

Piccolo,

Chen,

Louey

et al. 2024

Clinical Science

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In preterm neonates unable to obtain sufficient oral nutrition, intravenous lipid emulsion is life-saving. The contribution of post-conceptional level of maturation to pathology that some neonates experience is difficult to untangle from the global pathophysiology of premature birth. In this study we determined fetal physiological responses to intravenous lipid emulsion. METHODS Fetal sheep were given intravenous Intralipid 20® (n=4 female, 7 male) or Lactated Ringer’s Solution (n=7 female, 4 male) between 125±1 and 133±1 d of gestation (term=147 d). Manufacturer recommendation for premature human infants was followed: 0.5-1 g/kg/d initial rate, increased by 0.5-1 g/kg/d to 3 g/kg/d. Hemodynamic parameters and arterial blood chemistry were measured, and organs were studied postmortem. Red blood cell lipidomics were analyzed by LC-MS. RESULTS Intravenous intralipid did not alter hemodynamic or most blood parameters. Compared to Controls, Intralipid infusion increased final day plasma protein (P=0.004; 3.5±0.3 vs. 3.9±0.2), albumin (P=0.031; 2.2±0.1 vs. 2.4±0.2), and bilirubin (P<0.001; conjugated: 0.2±0.1 vs. 0.6±0.2; unconjugated: 0.2±0.1 vs. 1.1±0.4). Circulating IGF-1 decreased following Intralipid infusion (P<0.001; 66±24 vs. 46±24). Compared to Control Oil Red O liver stains (median score 0), Intralipid-infused fetuses scored 108 (P=0.0009). Lipidomic analysis revealed uptake and processing of infused lipids into red blood cells, increasing abundance of saturated fatty acids. CONCLUSION The near-term fetal sheep tolerates intravenous lipid emulsion well, although lipid accumulates in the liver. Increased levels of unconjugated bilirubin may reflect increased red blood cell turnover or impaired placental clearance. Whether Intralipid is less well tolerated earlier in gestation remains to be determined.

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Section: Discussionmentioning

confidence: 99%

Physiological response to fetal intravenous lipid emulsion

Piccolo,

Chen,

Louey

et al. 2024

Clinical Science

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“…Several strategies were evaluated within the rodent hyperoxia model and particularly IGF1, FGF10 and PDGFAA proved efficacy to reduce the alterations in lung morphometry. But so far only the first candidate was tested within a clinical trial not intended for BPD as primary readout and the results from an ongoing phase II study are still awaited [ 33 – 36 ]. Within the panel of therapeutic approaches towards attenuating the inflammatory response in the immature lung, targeting the inflammasome prevailed so far best suited and proved efficient in several preclinical studies, but still awaits documentation of its safety and efficacy in the clinics.…”

Section: Discussionmentioning

confidence: 99%

Anti-CCL2 therapy reduces oxygen toxicity to the immature lung

Shahzad,

Dong,

Behnke

et al. 2024

Cell Death Discov.

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Oxygen toxicity constitutes a key contributor to bronchopulmonary dysplasia (BPD). Critical step in the pathogenesis of BPD is the inflammatory response in the immature lung with the release of pro-inflammatory cytokines and the influx of innate immune cells. Identification of efficient therapies to alleviate the inflammatory response remains an unmet research priority. First, we studied macrophage and neutrophil profiles in tracheal aspirates of n = 103 preterm infants <29 weeks´ gestation requiring mechanical ventilation. While no differences were present at birth, a higher fraction of macrophages, the predominance of the CD14+CD16+ subtype on day 5 of life was associated with moderate/severe BPD. Newborn CCL-2−/− mice insufficient in pulmonary macrophage recruitment had a reduced influx of neutrophils, lower apoptosis induction in the pulmonary tissue and better-preserved lung morphometry with higher counts of type II cells, mesenchymal stem cells and vascular endothelial cells when exposed to hyperoxia for 7 days. To study the benefit of a targeted approach to prevent the pulmonary influx of macrophages, wildtype mice were repeatedly treated with CCL-2 blocking antibodies while exposed to hyperoxia for 7 days. Congruent with the results in CCL-2−/− animals, the therapeutic intervention reduced the pulmonary inflammatory response, attenuated cell death in the lung tissue and better-preserved lung morphometry. Overall, our preclinical and clinical datasets document the predominant role of macrophage recruitment to the pathogenesis of BPD and establish the abrogation of CCL-2 function as novel approach to protect the immature lung from hyperoxic injury.

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Insulin-like growth factor-1 replacement therapy after extremely premature birth: An opportunity to optimize lifelong lung health by preserving the natural sequence of lung development

Cited by 2 publications

References 55 publications

Physiological response to fetal intravenous lipid emulsion

Physiological response to fetal intravenous lipid emulsion

Anti-CCL2 therapy reduces oxygen toxicity to the immature lung

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