Trial reportEuropean journal of immunology2016
Interleukin-1 antagonism moderates the inflammatory state associated with Type 1 diabetes during clinical trials conducted at disease onset.
Trial report in European journal of immunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 58 citations in OpenAlex.
- Treg gene signatures predict and measure type 1 diabetes trajectory.JCI insight · 2019Trial
- Application of monoclonal antibodies in diabetes: A bibliometric analysis from 2004-2024.Human vaccines & immunotherapeutics · 2025Article
- Immunotherapies for prevention and treatment of type 1 diabetes.Immunotherapy · 2025Review
- Monocytes in type 1 diabetes families exhibit high cytolytic activity and subset abundances that correlate with clinical progression.Science advances · 2024Article
- Autoimmune diseases: targets, biology, and drug discovery.Acta pharmacologica Sinica · 2024Review
- A standardized metric to enhance clinical trial design and outcome interpretation in type 1 diabetes.Nature communications · 2023Article
- Preclinical models for Type 1 Diabetes Mellitus - A practical approach for research.International journal of medical sciences · 2023Review
- Inflammation versus regulation: how interferon-gamma contributes to type 1 diabetes pathogenesis.Frontiers in cell and developmental biology · 2023Review
- Article
- Dendritic Cells and Their Immunotherapeutic Potential for Treating Type 1 Diabetes.International journal of molecular sciences · 2022Review
- IL-1β Implications in Type 1 Diabetes Mellitus Progression: Systematic Review and Meta-Analysis.Journal of clinical medicine · 2022Review
- Endogenous Levels of Gamma Amino-Butyric Acid Are Correlated to Glutamic-Acid Decarboxylase Antibody Levels in Type 1 Diabetes.Biomedicines · 2021Article
- The β Cell in Diabetes: Integrating Biomarkers With Functional Measures.Endocrine reviews · 2021Review
- The effect of low-dose IL-2 and Treg adoptive cell therapy in patients with type 1 diabetes.JCI insight · 2021Article
- Gout: a disease involved with complicated immunoinflammatory responses: a narrative review.Clinical rheumatology · 2020Review
- Muscle-Organ Crosstalk: The Emerging Roles of Myokines.Endocrine reviews · 2020Review
- Innate immune stimulation of whole blood reveals IFN-1 hyper-responsiveness in type 1 diabetes.Diabetologia · 2020Article
- Enteroviruses and T1D: Is It the Virus, the Genes or Both which Cause T1D.Microorganisms · 2020Review
- The Connexin 43 Regulator Rotigaptide Reduces Cytokine-Induced Cell Death in Human Islets.International journal of molecular sciences · 2020Article
- Prediction and Prevention of Type 1 Diabetes.Frontiers in endocrinology · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 5 countries.
Funding
Abstract
It was hypothesized that IL-1 antagonism would preserve β-cell function in new onset Type 1 diabetes (T1D). However, the Anti-Interleukin-1 in Diabetes Action (AIDA) and TrialNet Canakinumab (TN-14) trials failed to show efficacy of IL-1 receptor antagonist (IL-1Ra) or canakinumab, as measured by stimulated C-peptide response. Additional measures are needed to define immune state changes associated with therapeutic responses. Here, we studied these trial participants with plasma-induced transcriptional analysis. In blinded analyses, 70.2% of AIDA and 68.9% of TN-14 participants were correctly called to their treatment arm. While the transcriptional signatures from the two trials were distinct, both therapies achieved varying immunomodulation consistent with IL-1 inhibition. On average, IL-1 antagonism resulted in modest normalization relative to healthy controls. At endpoint, signatures were quantified using a gene ontology-based inflammatory index, and an inverse relationship was observed between measured inflammation and stimulated C-peptide response in IL-1Ra- and canakinumab-treated patients. Cytokine neutralization studies showed that IL-1α and IL-1β additively contribute to the T1D inflammatory state. Finally, analyses of baseline signatures were indicative of later therapeutic response. Despite the absence of clinical efficacy by IL-1 antagonist therapy, transcriptional analysis detected immunomodulation and may yield new insight when applied to other clinical trials.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.