Cytokine Adsorption to Polymyxin B-Immobilized Fiber: An in vitro Study.


Journal

Blood purification
ISSN: 1421-9735
Titre abrégé: Blood Purif
Pays: Switzerland
ID NLM: 8402040

Informations de publication

Date de publication:
2021
Historique:
received: 31 03 2020
accepted: 17 07 2020
pubmed: 8 9 2020
medline: 7 8 2021
entrez: 7 9 2020
Statut: ppublish

Résumé

Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) are episodes of acute respiratory worsening characterized by diffuse alveolar damage superimposed on usual interstitial pneumonia. Direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX-DHP) is reported to have beneficial effects on the respiratory status and outcome in patients with AE-IPF although its mechanism of action is not fully elucidated. To investigate whether and how the PMX-immobilized fiber (PMX-F) adsorbs cytokines because reduction of the serum levels of various cytokines has been noted in AE-IPF patients receiving PMX-DHP. The propensity of recombinant cytokines for adsorption onto PMX-F was examined by incubating cytokines with heparin-coated or uncoated PMX-F for 2 h at 37°C. Cytokines were quantitated by multiplex bead array assay or ELISA. Interleukin (IL)-8, RANTES, platelet-derived growth factor-bb, and transforming growth factor-β were substantially adsorbed onto PMX-F without heparin coating. The adsorbed cytokines could be eluted with PMX sulfate, indicating that the PMX moiety is involved in cytokine adsorption. Importantly, although IL-1β, monocyte chemoattractant protein-1, fibroblast growth factor 2, and vascular endothelial growth factor-A were adsorbed onto PMX-F to lesser extents, the adsorption was enhanced by heparin coating of PMX-F. Furthermore, heparin-coated PMX-F acquired the capability to adsorb IL-6, IL-12, and tumor necrosis factor α. An affinity of heparin to PMX was determined (Kd = 0.061 ± 0.032 mg/mL), which accounts for the enhanced cytokine adsorption onto PMX-F upon heparin coating. Various cytokines involved in inflammation, fibrosis, and vascular permeability were shown to be adsorbed onto PMX-F. Removal of multiple cytokines may be associated with positive impacts of PMX-DHP in patients with AE-IPF.

Sections du résumé

BACKGROUND
Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) are episodes of acute respiratory worsening characterized by diffuse alveolar damage superimposed on usual interstitial pneumonia. Direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX-DHP) is reported to have beneficial effects on the respiratory status and outcome in patients with AE-IPF although its mechanism of action is not fully elucidated.
OBJECTIVE
To investigate whether and how the PMX-immobilized fiber (PMX-F) adsorbs cytokines because reduction of the serum levels of various cytokines has been noted in AE-IPF patients receiving PMX-DHP.
METHODS
The propensity of recombinant cytokines for adsorption onto PMX-F was examined by incubating cytokines with heparin-coated or uncoated PMX-F for 2 h at 37°C. Cytokines were quantitated by multiplex bead array assay or ELISA.
RESULTS
Interleukin (IL)-8, RANTES, platelet-derived growth factor-bb, and transforming growth factor-β were substantially adsorbed onto PMX-F without heparin coating. The adsorbed cytokines could be eluted with PMX sulfate, indicating that the PMX moiety is involved in cytokine adsorption. Importantly, although IL-1β, monocyte chemoattractant protein-1, fibroblast growth factor 2, and vascular endothelial growth factor-A were adsorbed onto PMX-F to lesser extents, the adsorption was enhanced by heparin coating of PMX-F. Furthermore, heparin-coated PMX-F acquired the capability to adsorb IL-6, IL-12, and tumor necrosis factor α. An affinity of heparin to PMX was determined (Kd = 0.061 ± 0.032 mg/mL), which accounts for the enhanced cytokine adsorption onto PMX-F upon heparin coating.
CONCLUSIONS
Various cytokines involved in inflammation, fibrosis, and vascular permeability were shown to be adsorbed onto PMX-F. Removal of multiple cytokines may be associated with positive impacts of PMX-DHP in patients with AE-IPF.

Identifiants

pubmed: 32894831
pii: 000510290
doi: 10.1159/000510290
doi:

Substances chimiques

Coated Materials, Biocompatible 0
Cytokines 0
Polymyxin B J2VZ07J96K

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

230-237

Informations de copyright

© 2020 S. Karger AG, Basel.

Auteurs

Toshiaki Utsunomiya (T)

Department of Clinical Research, National Hospital Organization Yamaguchi Ube Medical Center, Ube, Japan.
Department of Medicine and Clinical Science, Division of Cardiology, Yamaguchi University Graduate School of Medicine, Ube, Japan.

Yuka Mimura-Kimura (Y)

Department of Clinical Research, National Hospital Organization Yamaguchi Ube Medical Center, Ube, Japan.

Takeshi Yamamoto (T)

Department of Medicine and Clinical Science, Division of Cardiology, Yamaguchi University Graduate School of Medicine, Ube, Japan.

Keisuke Aoe (K)

Department of Clinical Research, National Hospital Organization Yamaguchi Ube Medical Center, Ube, Japan.

Keiji Oishi (K)

Department of Clinical Research, National Hospital Organization Yamaguchi Ube Medical Center, Ube, Japan.

Haruhito Kamei (H)

Department of Clinical Research, National Hospital Organization Yamaguchi Ube Medical Center, Ube, Japan.

Kazuto Matsunaga (K)

Department of Respiratory Medicine and Infectious Disease, Yamaguchi University Graduate School of Medicine, Ube, Japan.

Masafumi Yano (M)

Department of Medicine and Clinical Science, Division of Cardiology, Yamaguchi University Graduate School of Medicine, Ube, Japan.

Yusuke Mimura (Y)

Department of Clinical Research, National Hospital Organization Yamaguchi Ube Medical Center, Ube, Japan, mimura.yusuke.qy@mail.hosp.go.jp.

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Classifications MeSH