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Peer-reviewedCC BY 4.0Frontiers in Immunology

Supernatants from stored platelet concentrates modulate the inflammatory response in platelet-depleted blood ex vivo

10 affiliations
  1. 1Linnaeus Centre for Biomaterials Chemistry, Linnaeus University, Kalmar, Sweden.
  2. 2Department of Chemistry and Biomedicine, Linnaeus University, Kalmar, Sweden.
  3. 3Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
  4. 4Healthcare Research Strategy Department, Region Östergötland, Linköping, Sweden.
  5. 5Mayo Clinic Vaccine Research Group, Mayo Clinic, Rochester, MN, United States.
  6. 6Department of Clinical Chemistry and Transfusion Medicine, Region Kalmar County, Kalmar, Sweden.
  7. 7Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection, Linköping University, Linköping, Sweden.
  8. 8Cardiovascular Research Centre, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
  9. 9Department of Immunology, Oslo University Hospital and University of Oslo, Oslo, Norway.
  10. 10Research Laboratory, Nordland Hospital, Bodo, Norway.

Abstract

Introduction: Platelets contain a wide range of bioactive mediators, many of which accumulate during storage of platelet concentrates and have immunomodulatory properties. Our objective was to investigate how mediators derived from stored platelet concentrates modulate the acute inflammatory response using an ex vivo model.

Methods: Platelet-depleted whole blood from healthy donors (n=8) was supplemented with pooled platelet concentrate supernatants generated from six platelet concentrates sampled on storage days 1, 3, 5, and 7, and incubated with or without heat-inactivated Escherichia coli for four hours at 37 °C. Inflammatory responses were assessed by measuring complement activation, platelet-derived mediators, and cytokines.

Results: In the absence of E. coli , addition of platelet concentrate supernatants increased the levels of 24 of 32 measured inflammatory mediators. In contrast, under E. coli -stimulated conditions, the supernatants increased 10 markers and attenuated 14 markers, including the key pro-inflammatory cytokines IL-1β, IL-6, and TNF. The attenuation of these cytokines ranged from 25-43%, whereas several other mediators were unchanged or increased. The majority of biomarkers showed limited differences across the investigated storage time points.

Conclusions: Our findings demonstrate that soluble factors released from platelet concentrates can modulate inflammatory responses in platelet-depleted blood in an ex vivo setting, with context-dependent, bidirectional, and selective immunomodulatory effects.

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BibTeX
@article{andersson2026supernatants,
  title = {{Supernatants from stored platelet concentrates modulate the inflammatory response in platelet-depleted blood ex vivo}},
  author = {Linnea I Andersson and Dick J Sjöström and Nahreen Tynngård and Camilla Mohlin and Huy Quang Quach and Ivar Tjernberg and Sofia Ramström and Tom Eirik Mollnes and Per H Nilsson},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1928875},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1928875/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Supernatants from stored platelet concentrates modulate the inflammatory response in platelet-depleted blood ex vivo
AU  - Linnea I Andersson
AU  - Dick J Sjöström
AU  - Nahreen Tynngård
AU  - Camilla Mohlin
AU  - Huy Quang Quach
AU  - Ivar Tjernberg
AU  - Sofia Ramström
AU  - Tom Eirik Mollnes
AU  - Per H Nilsson
PY  - 2026
DA  - 2026/10/05
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1928875
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1928875/full
AB  - Introduction: Platelets contain a wide range of bioactive mediators, many of which accumulate during storage of platelet concentrates and have immunomodulatory properties. Our objective was to investigate how mediators derived from stored platelet concentrates modulate the acute inflammatory response using an ex vivo model.  Methods: Platelet-depleted whole blood from healthy donors (n=8) was supplemented with pooled platelet concentrate supernatants generated from six platelet concentrates sampled on storage days 1, 3, 5, and 7, and incubated with or without heat-inactivated Escherichia coli for four hours at 37 °C. Inflammatory responses were assessed by measuring complement activation, platelet-derived mediators, and cytokines.  Results: In the absence of E. coli , addition of platelet concentrate supernatants increased the levels of 24 of 32 measured inflammatory mediators. In contrast, under E. coli -stimulated conditions, the supernatants increased 10 markers and attenuated 14 markers, including the key pro-inflammatory cytokines IL-1β, IL-6, and TNF. The attenuation of these cytokines ranged from 25-43%, whereas several other mediators were unchanged or increased. The majority of biomarkers showed limited differences across the investigated storage time points.  Conclusions: Our findings demonstrate that soluble factors released from platelet concentrates can modulate inflammatory responses in platelet-depleted blood in an ex vivo setting, with context-dependent, bidirectional, and selective immunomodulatory effects.
SN  - 1664-3224
ER  -