Polarized Th2 Cytokine Production in Patients with Hypertrophic Scar Following Thermal Injury
Why this work is in the frame
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Bibliographic record
Abstract
Following thermal injury, hypertrophic scar (HSc) is a frequent and severe form of fibrosis of the skin, which limits movement and compromises the cosmetic appearance and function of the skin. Prolonged pruritus and dysesthesia are also common problems in the previously injured, fibrotic tissues, as current understanding of the pathogenesis is limited, and few effective therapies exist, as with other fibroproliferative disorders (FPD). To investigate the role of T cells and their cytokines in the development of HSc, intracellular cytokine synthesis of circulating T cells was measured serially in burn patients using flow cytometry from the time of injury to over a 1-year period during which many patients developed HSc. Within 1 month of injury, low interferon-gamma (IFN-gamma)-positive T cells (Th1) were found in association with low interleukin-12 (IL-12) and absent IFN-gamma cytokine levels in the serum. IL-4-positive Th 2 cells, however, were significantly increased compared with normal controls by 2 months postinjury. In burn patients with HSc, serum IL-10 and transforming growth factor-beta (TGF-beta) levels were also significantly increased early after burn injury in patients who later developed HSc compared with normal volunteers and with a subset of burn patients who did not develop HSc, before returning to normal levels after 6 months. Activated peripheral blood mononuclear cells (PBMC) demonstrated that mRNA for IFN-gamma was present only in normal volunteers or patients without HSc but was undetectable in HSc patients. IL-4 mRNA levels were increased in the PBMCs of burn patients with HSc. In HSc tissues, IL-4 mRNA was increased, whereas, IFN-gamma mRNA was reduced compared with normal skin and mature scar. Increased CD3(+) and CD4(+) cells were present in HSc tissues compared with normal skin and were coexpressed with the fibrogenic cytokine TGF-beta. These longitudinal studies in human patients with HSc suggest that fibrosis in the skin is associated with a polarized Th2 systemic response to injury that leads to increased T cells and their Th2 fibrogenic cytokines in tissues and the development of fibrosis and HSc.
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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 | 0.002 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.000 | 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 it