Reduced tissue macrophage population in the lung by anticancer agent cyclophosphamide: restoration by local granulocyte macrophage–colony-stimulating factor gene transfer
Bibliographic record
Abstract
Granulocytopenia is thought to be the sole mechanism underlying the increased susceptibility to bacterial infection in hosts with anticancer chemotherapy. Little is known about the functional state of tissue macrophage populations in such hosts. Using a model of chemotherapy-induced leukopenia, the number and function of alveolar macrophages (AMS) were examined during and after multiple injections of an anticancer agent, cyclophosphamide (CP). Although CP quickly reduced peripheral blood leukocytes, the number of these cells rebounded quickly 3 to 4 days after the withdrawal of CP. Accompanying blood leukopenia was a profound reduction in the number of AMs. Contrary to the rapid onset of blood leukopenia, tissue macrophage deficiency was a more chronic process that worsened gradually as the CP regimen continued. Of importance, in contrast to blood leukopenia, which restored itself shortly after CP withdrawal, tissue macrophage deficiency was not immediately self-recoverable in spite of a restored number of circulating leukocytes. Although AMS had a decreased ability to proliferate during, but not after, the CP regimen, these cells retained a normal ability to release tumor necrosis factor-alpha and nitric oxide. To identify the potential therapeutics for recovering macrophages, a gene vector expressing granulocyte macrophage-colony-stimulating factor (GM-CSF) was delivered either systemically or locally. GM-CSF transgene was able to expand macrophage populations only when delivered to the lung after, but not during, the CP regimen. This study thus identifies tissue macrophage deficiency as a mechanism of weakened innate immunity by chemotherapy and suggests the usefulness of topical GM-CSF transgene expression for restoring innate immunity in the lung.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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) | 0.001 | 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".