A166 THE LONG-LIVED ANTI-COLITIC EFFECT OF ADOPTIVE TRANSFER OF INTERLEUKIN-4 EDUCATED MACROPHAGES
Bibliographic record
Abstract
Postulating that cellular immunotherapy could be used to treat IBD, we showed that intraperitoneal (ip) injection of murine bone-marrow derived macrophages (BMDM) treated with IL-4 (M(IL4), i.e. alternatively activated macrophages), reduced the severity of dinitrobenzene sulphonic acid (DNBS)-induced colitis. Here we investigated the longevity of this response and queried a role for the microbiota in the inhibition of colitis evoked by the adoptive transfer of M(IL4)s. BMDM were treated with IL-4 (20 ng/mL, 48h) and 106 M(IL4)s were given to Balb/c mice (n=5–21, 1–3 experiments) by ip. injection 2, 5, 8 or 14 days prior to intra-rectal (ir) delivery of 3 mg of DNBS. Three days post-DNBS, mice were necropsied and disease severity assessed by macroscopic and histological disease scores. Other mice received a 1-week broad spectrum antibiotic (Abx) regimen in their drinking water and DNBS ± M(IL4)s 2 days prior to the DNBS. DNBS-treated mice consistently displayed loss of body weight, shortening of the colon, significant histopathology and disease activity scores (DAS) of 3.6 ± 0.9 (mean±SD, n=21; max. score is 5). M(IL4)s given 2 days prior to DNBS suppressed colitis, and remarkably mice treated with M(IL4)s 14 days before ir. DNBS were equally protected (DAS=1.5 ± 0.9, n=7), although some mice still displayed significant histopathology. In addition, M(IL4)s (2-day pretreatment) failed to ameliorate DNBS-induced colitis in mice concomitantly treated with antibiotics (DAS: control = 0 ± 8; DNBS = 3.6 ± 1.3; DNBS+M(IL4) = 0.9 ± 1.2; DBNS+M(IL4)+Abx = 3.3 ± 1.2; n=8–12, 3 experiments). These data provide proof-of-concept support for M(IL4) immunotherapy to treat colitis and suggest that each treatment could protect the individual for a considerable period of time. There are caveats with the use of antibiotics, nevertheless, these preliminary findings suggest that consideration of the gut microbiota may be needed in the translation of M(IL4) therapy for a targeted cohort of patients with IBD. CCC, CIHR
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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) | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".