Reversing Ongoing Chronic Intestinal Inflammation and Fibrosis by Sustained Block of IL-12 and IL-23 Using a Vaccine in Mice
Bibliographic record
Abstract
Interleukin (IL)-12 and IL-23 that share subunit p40 are important cytokines in the pathogenesis of inflammatory bowel disease. We reported that mouse p40 peptide-based vaccines ameliorated intestinal inflammation in the prevention of trinitrobenzene sulfonic acid (TNBS)–induced murine colitis model. Here, we evaluated whether administration of the vaccine after establishment of colitis would be effective in modifying both TNBS-induced and dextran sulfate sodium (DSS)–induced chronic colitis and the underlying immune mechanisms. We further examined whether vaccination could exacerbate infections. Chronic colitis was developed by either intrarectally administrating TNBS or drinking 4% DSS water. Vaccination started after two TNBS administrations or 7 days of DSS treatment. Results showed that administrating p40 vaccine induced high tittered antibodies to IL-12 and IL-23, improved clinical scores, reduced intestinal inflammation and fibrosis, and down-regulated proinflammatory cytokine productions in colon tissue, compared with control mice. Furthermore, in lamina propria mononuclear cells and/or mesenteric lymph nodes, mice immunized with p40 peptide vaccine exhibited high ratios of Treg/Th1 and Treg/Th17 cells and increased IL-10 expression in CD11c+IL-10+cells. In mice infected with lung chlamydia, in which the protective role of Th1/Th17 is well documented, vaccine immunization did not increase lung bacterial burden. We conclude that p40 vaccine may provide a potential and safe approach for treatment of IBD.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| 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".