Modulatory effect of IL‐1 inhibition following lipopolysaccharide‐induced neuroinflammation in neonatal microglia and astrocytes
Bibliographic record
Abstract
INTRODUCTION: Inflammation-induced white matter injury (WMI) in preterm infants is characterized by microglia activation, astrogliosis, oxidative stress and neurodevelopmental impairments. Microglia and astrocytes activation can be described under a broad spectrum of activation profile with extremes described as pro-inflammatory/neurotoxic (M1 microglia or A1 astrocyte) or anti-inflammatory/neuroprotective (M2 microglia or A2 astrocyte) in response to stimuli including lipopolysaccharide (LPS) and interleukin 1 (IL-1). As IL-1 signalling pathway has been posited as a major driver of inflammation-induced perinatal WMI, our aim was to evaluate the contribution of IL-1 modulation in LPS-induced microglia and astrocyte activation. METHODS: Primary neonatal cell co-cultures of astrocytes and microglia were treated with LPS (100 ng/ml) for 8 h or 24 h. Two distinct IL-1 receptor antagonists, Rytvela or Kineret (1 μg/ml), were added simultaneously with LPS to respectively modulate or block IL-1 receptor. Medium was collected to measure levels of IL-1β. Expression of markers related to pro- and anti-inflammatory microglia and astrocyte activation profiles and antioxidant genes were assessed. RESULTS: At 8 h, LPS exposure induced pro- (M1/A1) and anti-inflammatory (M2/A2) marker expression and inhibited antioxidant gene expression in microglia and astrocytes. By 24 h, continuous LPS exposure increased pro-inflammatory and neurotoxic microglial and astrocytic markers (M1/A1), as well as antioxidant genes. Administration of IL-1 antagonists Rytvela and Kineret with continuous LPS exposure had no significant effect on modulation of specific microglia and astrocyte activation pathways. DISCUSSION/CONCLUSION: We show that LPS effects on in vitro neonatal microglia and astrocytes co-cultures are time dependent eliciting a number of pro- and anti-inflammatory responses during the acute phase of inflammation (8 h), which shift towards pro-inflammatory and neurotoxic factors by 24 h. Although LPS-induced inflammation led to abundant IL-1 expression, IL-1 inhibition had no significant impact on in vitro modulation of microglia and astrocyte activation pathways towards M2 and A2 activation profile.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".