Abstract
BackgroundTh2 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.MethodologyThe 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.ResultsBinding 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, effects were found for tissue leukocytes and mucus hyper‐secretion. The anti‐inflammatory effects of PPS compared favorably with established topical nasal steroid treatment.ConclusionThis study points out PPS as a potent Th2 cytokine‐binding molecule with biological neutralization capacity and broad anti‐inflammatory effects in vivo. As such PPS fulfills the role as a potential candidate molecule for the treatment of AR and further studies of clinical efficacy seems highly warranted.
Highlights
Allergic rhinitis (AR) is an inflammatory disease of the upper airways with a global effect on a large subpopulation of individuals and impacting profoundly on the health and occupational productivity [1, 2].The development of an allergic inflammation is orchestrated by a variety of cell mediators
The affinity of the binding of IL-4, IL-5, and IL-13 to pentosan polysulfate sodium (PPS) was determined by estimating the amount of PPS, required to inhibit cytokine binding to the heparin coupled biosensor surface
The present study reveals several novel aspects regarding the capacity of PPS to modify an allergic response
Summary
Allergic rhinitis (AR) is an inflammatory disease of the upper airways with a global effect on a large subpopulation of individuals and impacting profoundly on the health and occupational productivity [1, 2].The development of an allergic inflammation is orchestrated by a variety of cell mediators. 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. Cytokine binding translated to a biological neutralization as PPS dose dependently inhibited Th2-dependent cell proliferation. Conclusion: This study points out PPS as a potent Th2 cytokine-binding molecule with biological neutralization capacity and broad anti-inflammatory effects in vivo. As such PPS fulfills the role as a potential candidate molecule for the treatment of AR and further studies of clinical efficacy seems highly warranted
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