Early life immune challenge alters innate immune responses to lipopolysaccharide: implications for host defense as adults
Bibliographic record
Abstract
Fever is the most common manifestation of the innate immune response to invading pathogens. Animals prevented from developing fever have increased morbidity and mortality to infection. We now show that early life events can program this innate immune response, in that rats that have been challenged neonatally with the immune stimulant lipopolysaccharide (LPS) have both suppressed febrile responses to LPS as adults and significantly reduced nuclear factor (NF)-kappaB activation in peripheral immune organs. This was associated with reduced levels of proinflammatory cytokines tumor necrosis factor (TNF)-alpha, and interleukin-6 (IL-6) in the plasma after adult LPS challenge, compared with animals that have received saline neonatally. In contrast, adult LPS challenge elicited higher corticosterone levels in the animals that had been treated neonatally with LPS. When this increased corticosterone response was negated by adrenalectomy or by administration of the glucocorticoid receptor antagonist RU-486, both the cytokine and febrile responses were normalized. This study indicates that the innate immune response can be programmed by a neonatal LPS challenge, whereby an amplified hypothalamic-pituitary-adrenal response causes reduced cytokine synthesis and an attenuated febrile response to an adult immune challenge. In light of the importance of fever in the host defense response, these alterations may have deleterious consequences on an individual's ability to combat disease later in life.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.002 |
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".