Bilirubin Possesses Powerful Immunomodulatory Activity and Suppresses Experimental Autoimmune Encephalomyelitis
Bibliographic record
Abstract
Bilirubin, an abundant bile pigment in mammalian serum, was once considered a toxic waste product and has more recently been recognized as a potent antioxidant of physiological importance. However, its potential biological functions in other fields are not well understood. Herein we show that bilirubin is also a powerful immunomodulatory agent. Bilirubin significantly inhibited Ag-specific and polyclonal T cell responses, while other similar antioxidants completely lacked this effect. Bilirubin suppressed CD4(+) T cell responses at multiple steps. High levels of bilirubin could induce apoptosis in reactive CD4(+) T cells. Bilirubin at nonapoptotic concentrations suppressed CD4(+) T cell reactivity through a wide range of actions, including inhibition of costimulator activities, suppression of immune transcription factor activation, and down-regulation of inducible MHC class II expression. Further studies suggest that bilirubin actions were direct, rather than via induction of immune deviation or regulatory T cells. In vivo, treatment with bilirubin effectively suppressed experimental autoimmune encephalomyelitis in SJL/J mice. In contrast, depletion of endogenous bilirubin dramatically exacerbated this disease. In summary, our results identify bilirubin as an important immunomodulator that may protect mammals against autoimmune diseases, thereby indicating its potential in the treatment of multiple sclerosis and other immune disorders.
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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".