Evidence mapPaperPMID 41799191Full record

ArticleTheranostics2026

Systemic Interleukin-4 Application Promotes Functional Recovery and Reprograms Neuroinflammatory and Molecular Responses after Spinal Cord Injury in Rats.

Obada Taleb Alhalabi, Stefan Heene, Guoli Zheng, Raban Heller, Tim Schubert, Marcin Luzarowski, Xiaowei Zha, Johannes Walter, Lea Hansen-Palmus, Bahram Biglari and 9 more

Abstract read
In one paragraph

Article in Theranostics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Obada Taleb AlhalabiDepartment of Neurosurgery, Heidelberg University Hospital, INF 400, 69120 Heidelberg, Germany.
Stefan HeeneDepartment of Neurosurgery, Heidelberg University Hospital, INF 400, 69120 Heidelberg, Germany.
Guoli ZhengDepartment of Neurosurgery, Heidelberg University Hospital, INF 400, 69120 Heidelberg, Germany.
Raban HellerInstitute for Experimental Endocrinology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Anna-Louisa-Karsch-Straße 2, 10178 Berlin, Germany.
Tim SchubertInstitute of Human Genetics, Heidelberg University, INF 366, 69120 Heidelberg, Germany.
Marcin LuzarowskiCore Facility for Mass Spectrometry and Proteomics, Center for Molecular Biology at Heidelberg University (ZMBH), INF 329, 69120 Heidelberg, Germany.
Xiaowei ZhaDepartment of Neurosurgery, Heidelberg University Hospital, INF 400, 69120 Heidelberg, Germany.
Johannes WalterDepartment of Neurosurgery, Heidelberg University Hospital, INF 400, 69120 Heidelberg, Germany.
Lea Hansen-PalmusInstitute of Virology, Technical University of Munich, Helmholtz Munich, Trogerstr. 30 81675 Munich, Germany.
Bahram BiglariDepartment of Paraplegiology, BG Trauma Centre Ludwigshafen, Ludwig-Guttmann-Straße 13, 67071 Ludwigshafen, Germany.
Xing-Jin WangDepartment of Neurosurgery, Heidelberg University Hospital, INF 400, 69120 Heidelberg, Germany.
Laura RuebenackerDepartment of Neurosurgery, Heidelberg University Hospital, INF 400, 69120 Heidelberg, Germany.
Thomas SkutellaDepartment of Neuroanatomy, Institute for Anatomy and Cell Biology, University of Heidelberg, INF 307, Heidelberg, Germany.
Karl KieningDepartment of Neurosurgery, Heidelberg University Hospital, INF 400, 69120 Heidelberg, Germany.
Christian Patrick SchaafInstitute of Human Genetics, Heidelberg University, INF 366, 69120 Heidelberg, Germany.
Sandro Manuel KriegDepartment of Neurosurgery, Heidelberg University Hospital, INF 400, 69120 Heidelberg, Germany.
Andreas Wilhelm UnterbergDepartment of Neurosurgery, Heidelberg University Hospital, INF 400, 69120 Heidelberg, Germany.
Klaus ZweckbergerDepartment of Neurosurgery, Heidelberg University Hospital, INF 400, 69120 Heidelberg, Germany.
Alexander YounsiDepartment of Neurosurgery, Heidelberg University Hospital, INF 400, 69120 Heidelberg, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Rationale: Traumatic spinal cord injury (SCI) initiates a cascade of local and systemic inflammatory events that exacerbate tissue damage, hinder regeneration, and impair functional recovery. Interleukin-4 (IL-4) is an anti-inflammatory cytokine that promotes M2-macrophage polarization, but its functional benefit in SCI and the underlying mechanisms remain incompletely defined. We evaluated whether systemic IL-4 therapy can enhance recovery and modulate neuroinflammation in a rat model of SCI, and examined the translational relevance of key cytokine signatures in human SCI. Methods: Female Wistar rats (n = 120) were randomized to sham surgery, SCI with vehicle, or SCI with IL-4 treatment. SCI was induced at T10 by clip contusion-compression; IL-4 (0.5 µg/kg) or vehicle was administered intraperitoneally twice daily for up to 7 days post-injury (dpi). Functional recovery was assessed with the Basso-Beattie-Bresnahan (BBB) scale, CatWalk XT gait analysis, and gridwalk testing. Spinal cords collected at 1, 3, 7, 14, and 28 dpi underwent immunohistochemistry, RNA sequencing, and proteomic profiling. Serum cytokines were quantified in rats by bead-based multiplex assays and compared with longitudinal cytokine profiles from SCI patients. Results: IL-4-treated rats demonstrated significantly improved BBB scores and multiple CatWalk XT gait parameters by 14 dpi versus vehicle. RNA-seq and proteomics identified upregulation of pathways related to axonogenesis, tissue repair, and reduced TNF-α-mediated pro-inflammatory signaling. Immunohistochemistry confirmed increased IBA1⁺/ARG1⁺ and IBA1⁺/CD206⁺ M2-macrophages, reduced IBA1⁺/iNOS⁺ M1-macrophages, smaller cystic cavity area, and higher APC⁺ oligodendrocyte counts in IL-4-treated animals. Serum profiling showed suppression of acute/subacute pro-inflammatory cytokine surges (1-7 dpi) with IL-4. In SCI patients, lower circulating levels of these cytokines were associated with better neurological outcomes. Conclusions: Repeated systemic IL-4 administration after SCI promotes functional recovery, shifts macrophage polarization toward a regenerative phenotype, reduces astrogliosis and oligodendrocyte loss, and suppresses systemic inflammation. Multi-omics integration together with patient data suggests IL-4 targets convergent pathways of neuroprotection and immune modulation, supporting its further development as a therapeutic candidate for SCI.

Indexed as

Interleukin-4Neuroinflammatory DiseasesRecovery of FunctionSpinal Cord InjuriesAnimalsCytokinesDisease Models, AnimalFemaleHumansInflammationMacrophagesRatsRats, WistarSpinal CordCytokinesInterleukin-4cytokinesfunctional recoveryIL-4neuroinflammationSpinal cord injurytranscriptomics

Identifiers

PMID41799191
PMCPMC12964225

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.