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

Blood Purif. 2021;50(2):230-237. doi: 10.1159/000510290. Epub 2020 Sep 7.

Abstract

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.

Keywords: Acute exacerbation of idiopathic pulmonary fibrosis; Diffuse alveolar damage; Heparin; Polymyxin B-immobilized fiber.

MeSH terms

  • Adsorption
  • Coated Materials, Biocompatible / chemistry
  • Cytokines / blood
  • Cytokines / isolation & purification*
  • Hemoperfusion / instrumentation
  • Hemoperfusion / methods*
  • Humans
  • Idiopathic Pulmonary Fibrosis / blood
  • Idiopathic Pulmonary Fibrosis / therapy*
  • Polymyxin B / chemistry*

Substances

  • Coated Materials, Biocompatible
  • Cytokines
  • Polymyxin B