PDF herunterladen
J Pediatr Intensive Care 2020; 09(03): 225-232
DOI: 10.1055/s-0040-1709994
Rapid Communication
Georg Thieme Verlag KG Stuttgart · New York

Chitin Analog AVR-25 Prevents Experimental Bronchopulmonary Dysplasia

Pragnya Das   **
1   Department of Pediatrics, Division of Neonatology, Drexel University, Philadelphia, Pennsylvania, United States
,
Suchismita Acharya   **
2   Acceleration Laboratory, University of North Texas Health Science Center, Fort Worth, Texas, United States
3   AyuVis Research Inc, Fort Worth, Texas, United States
,
Dilip Shah   *
1   Department of Pediatrics, Division of Neonatology, Drexel University, Philadelphia, Pennsylvania, United States
,
Beamon Agarwal
4   GenomeRxUS, Secane, Pennsylvania, United States
,
Varsha Prahaladan   *
1   Department of Pediatrics, Division of Neonatology, Drexel University, Philadelphia, Pennsylvania, United States
,
Vineet Bhandari   *
1   Department of Pediatrics, Division of Neonatology, Drexel University, Philadelphia, Pennsylvania, United States
› Institutsangaben Funding This work was partly supported by a research contract grant received from AyuVis Research Inc.
Weitere Informationen

Publikationsverlauf

13. Februar 2020

27. März 2020

Publikationsdatum:
08. Mai 2020 (online)

    Lizenzen und Reprints

Abstract

Infants born extremely preterm are at a high risk of developing bronchopulmonary dysplasia (BPD) which is characterized by large, simplified alveoli, increased inflammation, disrupted and dysregulated vasculogenesis, decreased cell proliferation, and increased cell death in the lungs. Due to lack of specific drug treatments to combat this condition, BPD and its long-term complications have taken a significant toll of healthcare resources. AVR-25, a novel immune modulator experimental compound, was able to partially recover the pulmonary phenotype in the hyperoxia-induced experimental mouse model of BPD. We anticipate that AVR-25 will have therapeutic potential for managing human BPD.

Keywords

bronchopulmonary dysplasia - interleukin-10 - anti-inflammatory

* Current affiliation: Cooper Health University and Hospital, Suite 206, 401 Haddon Avenue, Education and Research Building, Camden, NJ 08103, USA.


** These authors contributed equally to this article.


Authors' Contributions

P.D., S.A., B.A., and V.B. conceptualized and designed the study, drafted the initial manuscript, and submitted as approved; P.D., S.A., D.S., B.A., and V.P. performed the initial experiments. All the authors approved the final manuscript.


 

  • References

  • 1 Balany J, Bhandari V. Understanding the impact of infection, inflammation, and their persistence in the pathogenesis of bronchopulmonary dysplasia. Front Med (Lausanne) 2015; 2: 90
    PubMedGoogle Scholar
  • 2 Bhandari V. Drug therapy trials for the prevention of bronchopulmonary dysplasia: current and future targets. Front Pediatr 2014; 2: 76
    PubMedGoogle Scholar
  • 3 Russell RB, Green NS, Steiner CA. , et al. Cost of hospitalization for preterm and low birth weight infants in the United States. Pediatrics 2007; 120 (01) e1-e9
    CrossrefPubMedGoogle Scholar
  • 4 Jobe AH. Mechanisms of lung injury and bronchopulmonary dysplasia. Am J Perinatol 2016; 33 (11) 1076-1078
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 5 Smith VC, Zupancic JA, McCormick MC. , et al. Trends in severe bronchopulmonary dysplasia rates between 1994 and 2002. J Pediatr 2005; 146 (04) 469-473
    CrossrefPubMedGoogle Scholar
  • 6 Trembath A, Laughon MM. Predictors of bronchopulmonary dysplasia. Clin Perinatol 2012; 39 (03) 585-601
    CrossrefPubMedGoogle Scholar
  • 7 Gentner S, Laube M, Uhlig U. , et al. Inflammatory mediators in tracheal aspirates of preterm infants participating in a randomized trial of permissive hypercapnia. Front Pediatr 2017; 5: 246
    CrossrefPubMedGoogle Scholar
  • 8 Sureshbabu A, Syed M, Das P. , et al. Inhibition of regulatory-associated protein of mechanistic target of rapamycin prevents hyperoxia-induced lung injury by enhancing autophagy and reducing apoptosis in neonatal mice. Am J Respir Cell Mol Biol 2016; 55 (05) 722-735
    CrossrefPubMedGoogle Scholar
  • 9 Syed MA, Choo-Wing R, Homer RJ, Bhandari V. Role of nitric oxide isoforms in vascular and alveolar development and lung injury in vascular endothelial growth factor overexpressing neonatal mice lungs. PLoS One 2016; 11 (01) e0147588
    CrossrefPubMedGoogle Scholar
  • 10 Xia WS, Liu P, Zhang JL, Chen J. Biological activities of chitosan and chitooligosaccharides. Food Hydrocoll 2011; 25 (02) 170-179
    CrossrefPubMedGoogle Scholar
  • 11 Das P, Panda SK, Agarwal B. , et al. Novel chitohexaose analog protects young and aged mice from CLP induced polymicrobial sepsis. Sci Rep 2019; 9 (01) 2904
    CrossrefPubMedGoogle Scholar
  • 12 Panda SK, Kumar S, Tupperwar NC. , et al. Chitohexaose activates macrophages by alternate pathway through TLR4 and blocks endotoxemia. PLoS Pathog 2012; 8 (05) e1002717
    CrossrefPubMedGoogle Scholar
  • 13 Nair MG, Cochrane DW, Allen JE. Macrophages in chronic type 2 inflammation have a novel phenotype characterized by the abundant expression of Ym1 and Fizz1 that can be partly replicated in vitro. Immunol Lett 2003; 85 (02) 173-180
    CrossrefPubMedGoogle Scholar
  • 14 Salaets T, Aertgeerts M, Gie A. , et al. Preterm birth impairs postnatal lung development in the neonatal rabbit model. Respir Res 2020; 21 (01) 59
    CrossrefPubMedGoogle Scholar
  • 15 Frank L, Sosenko IR. Failure of premature rabbits to increase antioxidant enzymes during hyperoxic exposure: increased susceptibility to pulmonary oxygen toxicity compared with term rabbits. Pediatr Res 1991; 29 (03) 292-296
    CrossrefPubMedGoogle Scholar
  • 16 Leary S, Das P, Ponnalagu D, Singh H, Bhandari V. Genetic strain and sex differences in a hyperoxia-induced mouse model of varying severity of bronchopulmonary dysplasia. Am J Pathol 2019; 189 (05) 999-1014
    CrossrefPubMedGoogle Scholar
  • 17 Choo-Wing R, Syed MA, Harijith A. , et al. Hyperoxia and interferon-γ-induced injury in developing lungs occur via cyclooxygenase-2 and the endoplasmic reticulum stress-dependent pathway. Am J Respir Cell Mol Biol 2013; 48 (06) 749-757
    CrossrefPubMedGoogle Scholar
  • 18 Um-Bergström P, Hallberg J, Pourbazargan M. , et al. Pulmonary outcomes in adults with a history of bronchopulmonary dysplasia differ from patients with asthma. Respir Res 2019; 20 (01) 102
    CrossrefPubMedGoogle Scholar
  • 19 Thompson A, Bhandari V. Pulmonary biomarkers of bronchopulmonary dysplasia. Biomark Insights 2008; 3: 361-373
    PubMedGoogle Scholar
  • 20 Kolls JK. Commentary: understanding the impact of infection, inflammation and their persistence in the pathogenesis of bronchopulmonary dysplasia. Front Med (Lausanne) 2017; 4: 24
    PubMedGoogle Scholar
  • 21 Kim HY, Chang YJ, Subramanian S. , et al. Innate lymphoid cells responding to IL-33 mediate airway hyperreactivity independently of adaptive immunity. J Allergy Clin Immunol 2012; 129 (01) 216-27 e1–6
    CrossrefPubMedGoogle Scholar
  • 22 Berger J, Bhandari V. Animal models of bronchopulmonary dysplasia. The term mouse models. Am J Physiol Lung Cell Mol Physiol 2014; 307 (12) L936-L947
    CrossrefPubMedGoogle Scholar
  • 23 Harijith A. , B V. Hyperoxia in the pathogenesis of bronchopulmonary dysplasia. In Bronchopulmonary Dysplasia. Bhandari V. , ed. Switzerland: Springer International Publishing; 2016: 3-26
    Google Scholar
  • 24 Aghai ZH, Camacho J, Saslow JG. , et al. Impact of histological chorioamnionitis on tracheal aspirate cytokines in premature infants. Am J Perinatol 2012; 29 (07) 567-572
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 25 Nayeri UA, Buhimschi CS, Zhao G, Buhimschi IA, Bhandari V. Components of the antepartum, intrapartum, and postpartum exposome impact on distinct short-term adverse neonatal outcomes of premature infants: a prospective cohort study. PLoS One 2018; 13 (12) e0207298
    CrossrefPubMedGoogle Scholar
  • 26 Ambalavanan N, Carlo WA, D'Angio CT. , et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Cytokines associated with bronchopulmonary dysplasia or death in extremely low birth weight infants. Pediatrics 2009; 123 (04) 1132-1141
    CrossrefPubMedGoogle Scholar
  • 27 Vento G, Capoluongo E, Matassa PG. , et al. Serum levels of seven cytokines in premature ventilated newborns: correlations with old and new forms of bronchopulmonary dysplasia. Intensive Care Med 2006; 32 (05) 723-730
    CrossrefPubMedGoogle Scholar
  • 28 Garingo A, Tesoriero L, Cayabyab R. , et al. Constitutive IL-10 expression by lung inflammatory cells and risk for bronchopulmonary dysplasia. Pediatr Res 2007; 61 (02) 197-202
    CrossrefPubMedGoogle Scholar
  • 29 Sanin DE, Prendergast CT, Mountford AP. IL-10 production in macrophages is regulated by a TLR-driven CREB-mediated mechanism that is linked to genes involved in cell metabolism. J Immunol 2015; 195 (03) 1218-1232
    CrossrefPubMedGoogle Scholar