Abstract 007: Interleukin-6 Inhibition Attenuates Hypertension and Associated Renal Damage in Dahl Salt-sensitive (SS) Rats
Bibliographic record
Abstract
Data from our lab indicates that infiltration of T lymphocytes into the kidney amplifies salt-sensitive hypertension and renal damage in SS rats. Interestingly, interleukin 6 (IL-6) mRNA is >50-fold higher in T cells isolated from the kidney in comparison to circulating T cells. Experiments were performed to assess the role of IL-6 in Dahl SS rats (n=13-14/group) fed low salt chow until 9 weeks of age and subsequently treated with goat anti-rat IL-6 neutralizing antibody (anti-rIL-6; 4 μg /day, IP; R&D Systems, Minneapolis, MN) or normal goat IgG control (4 μg /day, IP) during an 11 day period of high salt intake. The MAP and urine albumin excretion rates (Ualb) were not different between the groups when fed low NaCl chow (MAP=121±1.6 mmHg versus 122±1.8 mmHg and Ualb=15±2mg/day versus 12±1.7 mg/day in the vehicle-treated versus anti-rIL-6-treated rats). Following 11 days of drug-treatment, the rats receiving anti-rIL-6 demonstrated a significant 47% reduction in IL-6 in the renal medulla compared to vehicle-treated SS. Moreover, the increase in MAP following 11 days of high NaCl intake was significantly attenuated in SS administered anti-rIL-6 (MAP=138±3 mmHg) compared with the control group (MAP=149±3 mmHg). The renal damage was also attenuated in SS administered anti-rIL-6; Ualb was significantly reduced in the treated (109±10 mg/day) compared to the control group (151±16 mg/day) and glomerular and tubular damage were also attenuated. To investigate potential mechanisms of action, a flow cytometric analysis of infiltrating immune cells in the kidney (n=4-5/group) was performed. The total number of leukocytes (CD45+) was significantly lower in the treatment vs the control group (4.8±0.5x106 vs 6.8±0.5x106 cells/kidney). Infiltrating monocytes and macrophages (CD11b/c+) were also significantly lower in the treatment vs the control group (3.7±0.3x106 vs 5.4±0.3x106 cells/kidney). The total number of infiltrating T and B lymphocytes was not different among the groups. The present studies indicate that IL-6 production may participate in the development of SS hypertension and end-organ damage by mediating the recruitment and infiltration of macrophages into the kidney.
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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) | 0.001 | 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 | 0.001 |
| 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 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".