Adiponectin rescues the newborn rat lung from lipopolysaccharide (LPS)‐induced inflammation and injury
Bibliographic record
Abstract
Introduction Preterm infants born during the canalicular and saccular stages of lung development are at high risk for lung injury from oxidative stress and inflammation. Low adipose tissue mass is associated with low serum levels of protective anti‐inflammatory and anti‐oxidative adipokines, such as adiponectin (APN). The modulatory role of APN on inflammatory cytokines and tissue remodeling has unveiled APN as a novel therapeutic target for developmental lung pathologies. We have previously shown that prophylactic administration of exogenous APN protects the newborn rat from LPS‐induced lung injury. In this study, we investigate the ability for systemic APN given 20 hours after LPS aspiration to reverse lung injury in newborn rats. Methods Sprague‐Dawley rats at postnatal day (PND) 4 were treated with 5 mg/kg intrapharyngeal (IPh) LPS or saline; 20 hours later, 2 mg/kg recombinant APN (rAPN) or equal volume saline was administered intraperitoneally (IP). The three treatment groups included: rats exposed to LPS (IPh)/rAPN (IP), LPS (IPh)/saline (IP) and saline (IPh)/saline (IP). Lungs were harvested 6 hours after administration of rAPN and processed for gene (qPCR) and protein (SDS‐PAGE Western blot) expression. In another cohort of PND4 rats, rAPN was administered at 20 and 44 hours, with lungs removed and assayed for histopathology with haemotoxylin and eosin staining 72 hours after LPS. n=4 in each treatment group for gene/protein expression and histopathology. Results Differences were observed in gene and protein expression between treatment groups (ANOVA, p<0.05). In animals treated with IP rAPN 20 hours after IPh LPS, mRNA expression of macrophage inflammatory protein‐1α ( MIP‐1 α ), monocyte chemoattractant protein‐1 ( MCP‐1 ) , IL‐1 β , IL‐6, and IL‐10 was reduced 7‐, 8‐, 3.6‐, 1.6‐ and 13‐fold, respectively, relative to saline treatment. Protein expression of tumor necrosis factor α (TNF‐α), IL‐1β and IL‐10 was also relatively reduced in rAPN treated rats. No change was detected in the mRNA expression of TNF‐ α , or in the protein expression of IL‐6. Lungs treated with rAPN had a marked reduction in histopathological changes relative to saline‐treated controls. Conclusions Our novel in vivo study demonstrates that beyond the preventative role of systemic APN in neonatal lung injury, APN can also attenuate previously induced acute, inflammatory lung injury. We speculate that increasing serum APN levels in preterm infants might protect from acute and chronic inflammatory lung injury. Support or Funding Information Women’s Auxiliary Board at SickKids
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".