Volatile Anesthetics Differentially Affect Immunostimulated Expression of Inducible Nitric Oxide Synthase
Bibliographic record
Abstract
BACKGROUND: Nitric oxide released by inducible nitric oxide synthase (iNOS) plays an important role in immune responses and systemic vasodilation in septic shock. Volatile anesthetics have been reported to interfere with signal transduction and gene expression. We studied the effect of volatile anesthetics on activity and expression of iNOS and potential mechanisms of action. METHODS: Nitrite release and iNOS expression were determined using the Griess reaction and Western and Northern blot techniques, respectively, in J774 murine macrophages stimulated with lipopolysaccharide and gamma-interferon in the absence and presence of various concentrations (0.25-2.0 minimum alveolar concentration [MAC]) of volatile anesthetics (i.e., halothane, enflurane, isoflurane, desflurane). Furthermore, potential interference of volatile anesthetics with specific signal transduction pathways was investigated. RESULTS: All volatile anesthetics, studied in a time- and dose-dependent manner, suppressed nitrite production and iNOS expression in J774 macrophages stimulated by lipopolysaccharide or gamma-interferon at clinically relevant concentrations. The inhibition was completely antagonized by ionomycin but unaffected by diacylglycerol, phorbol myristate acetate, and C2-ceramide. In contrast, in cells costimulated by lipopolysaccharide plus gamma-interferon, volatile anesthetics significantly increased nitrite production and iNOS expression independent of ionomycin and other mediators studied. CONCLUSIONS: Volatile anesthetics strongly reduced the mRNA and protein levels of iNOS and NOS activity after a single stimulation with lipopolysaccharide or gamma-interferon, most likely by attenuating intracellular calcium increase. Costimnulation with lipopolysaccharide plus gamma-interferon, however, results in maximum iNOS expression and activity, which are no longer inhibited but are potentiated by volatile anesthetics by unidentified mechanisms.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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 | 0.000 |
| 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 source (direct Gemma or distilled Codex), 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".