PXD065980

PXD065980 is an original dataset announced via ProteomeXchange.

Title	Systemic application of IL-4 attenuates secondary local inflammation processes and enhances functional recovery after traumatic spinal cord injury in rats.
Description	Background: Traumatic spinal cord injury (SCI) triggers local and systemic inflammation cascades, limiting neuroregeneration and impeding functional recovery. We investigated the systemic effect of immunomodulation with Interleukin-4 (IL-4) on the local immune reaction and regeneration in injured spinal cord tissue, in addition to the systemic cytokine landscape after SCI in rats. Methodology: After performing a T10 laminectomy, 120 female Wistar rats were randomized to either thoracic clip compression/contusion SCI or sham. SCI animals received intraperitoneal (i.p.) IL-4 or vehicle injections twice daily for up to 7 days post-injury (dpi). Rats underwent a battery of neurobehavioral tests and were sacrificed at 1, 3, 7, 14, and 28 dpi. Transcriptomcis, proteomics and immunohistochemistry (IHC) was used to assess macrophage polarization, cellular neurodegeneration, and astrogliosis of explanted spinal cords. High throughput seromics was applied to measure levels of 18 cytokines in rat serum, which were also compared to SCI patient serum data. Results: IL-4-treated rats showed a significantly better recovery in the Basso, Beattie, Bresnahan locomotor rating scale score and several Catwalk XT gait analysis parameters at 14 dpi. RNA-Seq and proteomics analyses revealed a significant upregulation in gene ontologies pertaining to improved axonogenisis and tissue repair along with reduced neuronal death and the pro-inflammatory TNFa signaling. This was verified via IHC, showing a higher abundance of IBA1+/ARG1+ and IBA1+/CD206+ M2-macrophages with a lower abundance of IBA1+/iNOS+ M1-macrophages compared to vehicle-treated rats at 3 dpi. Furthermore, post-traumatic cyst size was significantly reduced with IL-4 treatment at 28 dpi. While APC+ oligodendrocytes showed a significantly higher cell count in the IL-4 group, no significant difference was noted in NeuN+ neurons compared to the vehicle-treated group at 28 dpi. Seromics revealed significantly higher levels of pro-inflammatory serum cytokines in vehicle-treated rats compared to sham rats in the acute to subacute post-injury phase (1, 3 and 7 dpi), which were effectively suppressed by IL-4 treatment. Consistent with our rat model, data analysis of SCI patients revealed improved outcome of patients with low serum levels of pro-inflammatory cytokines reduced by IL-4. Conclusions: Intraperitoneal IL-4 treatment modulated local and systemic inflammation after SCI and improved functional recovery. Transcriptomic and proteomic profiling revealed activation of regenerative and neuroprotective pathways and suppression of pro-inflammatory signaling, supporting the histological and behavioral findings. These results provide mechanistic insight into IL-4’s effects and support its further preclinical evaluation in SCI.
HostingRepository	PRIDE
AnnounceDate	2026-03-16
AnnouncementXML	Submission_2026-03-16_04:49:31.852.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marcin Luzarowski
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: NEWT:10116;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-09 22:35:38	ID requested
⏵ 1	2026-03-16 04:49:32	announced

10.7150/thno.123815;

Alhalabi OT, Heene S, Zheng G, Heller R, Schubert T, Luzarowski M, Zha X, Walter J, Hansen-Palmus L, Biglari B, Wang XJ, Ruebenacker L, Skutella T, Kiening K, Schaaf CP, Krieg SM, Unterberg AW, Zweckberger K, Younsi A, Systemic Interleukin-4 Application Promotes Functional Recovery and Reprograms Neuroinflammatory and Molecular Responses after Spinal Cord Injury in Rats. Theranostics, 16(9):4726-4744(2026) [pubmed]

submitter keyword: Immunomodulation, CatWalk XT gait analysis, Seromics,Spinal Cord Injury, IL-4

Marcin Luzarowski
contact affiliation	Core Facility for Mass Spectrometry and Proteomics, Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany
contact email	m.luzarowski@zmbh.uni-heidelberg.de
lab head
Marcin Luzarowski
contact affiliation	University of Heidelberg
contact email	m.luzarowski@zmbh.uni-heidelberg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD065980
     1. Label: PRIDE project
     2. Name: Systemic application of IL-4 attenuates secondary local inflammation processes and enhances functional recovery after traumatic spinal cord injury in rats.