Acute phase response impairs host defense against Pseudomonas aeruginosa pneumonia in mice*
Bibliographic record
Abstract
OBJECTIVE: Pseudomonas aeruginosa is a common pathogen in hospital-acquired pneumonia. Especially trauma and postsurgical patients display a profound acute phase protein response and are susceptible to acquiring pneumonia. The objective was to study the influence of the acute phase response induced by sterile tissue injury on pulmonary host defense. DESIGN: Laboratory investigation. SETTING: Academic medical center. SUBJECTS: Female C57Bl/6 wild-type mice, 8-10 wks old. INTERVENTIONS: Mice were injected subcutaneously with either turpentine or sterile saline (control) in both hind limbs 1 day before intranasal infection with P. aeruginosa. MEASUREMENTS AND MAIN RESULTS: The turpentine-induced acute phase response was associated with 100% lethality after induction of pneumonia, whereas control mice all survived the Pseudomonas infection. In addition, turpentine-injected mice demonstrated much higher bacterial loads in their lungs and an increased dissemination of the infection. The acute phase reaction attenuated lung inflammation during pneumonia, as reflected by histopathology, reduced pulmonary levels of proinflammatory cytokines, and a strongly diminished recruitment of neutrophils to the site of infection. Blood neutrophils harvested from turpentine injected mice displayed a reduced capacity to up-regulate their CD11b/CD18 expression upon stimulation with Pseudomonas ex vivo and during Pseudomonas pneumonia in vivo. Administration of a blocking anti-CD11b antibody to turpentine-injected and control mice almost completely abrogated the difference in bacterial outgrowth, whereas inhibition of the sympathetic nervous system did not affect the impaired pulmonary host defense in mice with an acute phase response. CONCLUSIONS: These data suggest that a systemic acute phase response might impair host defense against P. aeruginosa pneumonia, possibly in part by inhibition of CD11b/CD18-dependent neutrophil recruitment.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 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".