Broad Th2 neutralization and anti-inflammatory action of pentosan polysulfate sodium in experimental allergic rhinitis

Immunity, Inflammation and Disease
Caroline SandenJonas S Erjefält

Abstract

Th2 cytokines like interleukin-4, -5, and -13 are regarded as important drivers of the immunopathology underlying allergic rhinitis (AR) and asthma. The present study explores the capacity of pentosan polysulfate sodium (PPS), a semi-synthetic heparin-like macromolecular carbohydrate, to bind Th2 cytokines and exert biological neutralization in vitro, as well as anti-inflammatory actions in vivo. The capacity of PPS to bind recombinant Th2 cytokines was tested with surface plasmon resonance (SPR) technology and biological Th2 neutralization was assessed by Th2-dependent proliferation assays. The in vivo anti-inflammatory action of PPS was studied using a validated Guinea-pig model of AR. Binding studies revealed a strong and specific binding of PPS to IL-4, IL-5, and IL-13 with IC values suggesting as stronger cytokine binding than for heparin. Cytokine binding translated to a biological neutralization as PPS dose dependently inhibited Th2-dependent cell proliferation. Topical administration of PPS 30 min prior to nasal allergen challenge of sensitized animals significantly reduced late phase plasma extravasation, luminal influx of eosinophils, neutrophils, and total lavage leukocytes. Similar, albeit not statistically secured,...Continue Reading

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Citations

Apr 5, 2019·American Journal of Rhinology & Allergy·Zhong BingLiu Shi-Xi
Jan 9, 2019·Frontiers in Neuroscience·Luke GrundyStuart M Brierley
May 16, 2020·International Journal of Molecular Sciences·Chun Hua PiaoOk Hee Chai
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Nov 1, 2017·Analytical Chemistry·Xuewei WangMark E Meyerhoff
Sep 29, 2021·Aktuelle Urologie·Andreas Wiedemann

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Methods Mentioned

BETA
surface plasmon resonance
chips
biosensor
lavage
protein assay
chip
FCS

Software Mentioned

GraphPad
GraphPad Prism

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