Anti-Inflammatory Effect of Recombinant Human Alpha-fetoprotein (rhAFP) in the Model of TNBS-induced Colitis
Bibliographic record
Abstract
Introduction: Management of IBD relies primarily on steroids, immunosuppressors and anti-TNF agents. Although effective, these drugs are associated with side effects and reduced quality of life. Safer and more effective therapies are needed. In a small placebo-controlled trial (78 pts) human AFP (hAFP) was reported to effectively reduce symptoms of IBD. After 30 days of treatment 100% of hAFP pts showed clinical improvement. 47% gained weight. Over 30% of Crohn's and colitis pts had regained normal bowel movement. Endoscopy confirmed decreased number of ulcerative lesions. Almost half of hAFP pts were able to reduce or stop steroid use while no changes occurred in placebo patients*. Phase I and 2 clinical trials of rhAFP demonstrated an excellent safety profile with no serious adverse events or immune reactions. Present study aimed to investigate the efficacy and mode of action of rhAFP in a model of TNBS-induced colitis. Methods: Colitis was induced by intrarectal infusion of TNBS in C57bl6 mice. Mice received either daily injections of saline IV, anti-TNFα 0.1 mg/mouse, IP starting 3 days prior to TNBS infusion or rhAFP 200 μg/day starting 1 day before colitis induction and until euthanasia on day 2 after induction (20 mice/group). Colonic inflammation was evaluated using Wallace and Ameho scores.Colonic MPO level as well as gene expression of pro- and anti-inflammatory cytokines (IL-1 β IL-6, IFNγ, TNFα, and IL-10) were also measured. Results: rhAFP administration significantly decreased colonic inflammation with a 40% reduction in Wallace score compared to saline group (Fig. 1). Ameho's score was significantly lower in rhAFP group than in anti-TNFα or saline groups (Fig. 2), while MPO level in the colon was reduced from 40.72±0.64 to 29.59±3.11 and 25.42±4.22 ng/mg protein in control, anti-TNFα and rhAFP groups, respectively. The effect of rhAFP on cytokine production was similar to that of anti-TNFα with significant reduction in gene expression for IL-1β, IL-6, IFNγ, and TNFα and a significant increase for IL-10 (Table 1).Figure: Evaluation of inflammation at the macroscopic level: Wallace's score.Figure: Evaluation of inflammation at the histological level: Ameho's score.Table: Table. Cytokine Gene Expression Levels (mRNA/GAPDH ratio)Conclusion: This study confirms strong anti-inflammatory activity of rhAFP in the TNBS model of colitis with efficacy similar or greater than anti-TNFα. Considering the exceptional safety profile of rhAFP this molecule offers the possibility of novel safe and effective treatment for patients with IBD. *Chereshnev V, et al. Alpha-Fetoprotein. Russian Academy of Sciences, 2004, 239-245.
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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) | 0.001 | 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) | 0.001 | 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".