Document Detail


Polymyxin B Agonist Capture Therapy for Intrauterine Inflammation: Proof-of-Principle in a Fetal Ovine Model.
MedLine Citation:
PMID:  24220658     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Intrauterine infection is a leading cause of preterm birth (PTB), most notably in deliveries occurring before 32 weeks gestation. Preterm infants exposed to intrauterine inflammation are more likely to have a host of neurological, respiratory, gastrointestinal, and visual pathologies. Preventing preterm delivery and protecting the fetus from injury is thus likely to require treatment of both intrauterine infection and inflammation. Polymyxin B (PMXB) is a cationic peptide antibiotic that binds Escherichia coli lipopolysaccharides (LPS) and prevents inflammatory activation. We hypothesized that intraamniotic administration of PMXB would selectively inhibit LPS-driven inflammation, serving as a proof-of-principle for targeted agonist capture therapy as a treatment for PTB and fetal injury. In vitro studies with primary fetal ovine keratinocytes demonstrated a significant and sustained reduction in tumor necrosis factor α and interleukin 8 messenger RNA expression after treatment with PMXB and LPS, relative to cells treated with LPS alone. In vivo studies with fetal sheep demonstrated a significant reduction in proinflammatory cytokines in the amniotic fluid and fetal lung (but not fetal skin or chorioamnion) in LPS + PMXB-treated animals, relative to those treated with LPS alone. These data are consistent with a partial resolution of LPS-driven intrauterine inflammation. They suggest the potential for agonist capture as a conceptual means of resolving the proparturition inflammation caused by infection of the amniotic cavity.
Authors:
Masatoshi Saito; Matthew S Payne; Yuichiro Miura; Demelza J Ireland; Sarah Stock; Suhas G Kallapur; Paranthaman S Kannan; John P Newnham; Boris W Kramer; Alan H Jobe; Jeffrey A Keelan; Matthew W Kemp
Related Documents :
9348248 - Transplacental needle passage and other risk-factors associated with second trimester a...
2403608 - Diagnostic and therapeutic technology assessment. chorionic villus sampling: a reassess...
1627058 - Chorionic villus sampling: evaluation of obstetric performance.
8487268 - Prenatal diagnosis of diastrophic dysplasia with polymorphic dna markers.
11111218 - Percutaneous laser ablation of fetal congenital cystic adenomatoid malformation: too li...
14634978 - Fetal serum alpha-fetoprotein in alloimmunised pregnancies.
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-11-12
Journal Detail:
Title:  Reproductive sciences (Thousand Oaks, Calif.)     Volume:  -     ISSN:  1933-7205     ISO Abbreviation:  Reprod Sci     Publication Date:  2013 Nov 
Date Detail:
Created Date:  2013-11-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101291249     Medline TA:  Reprod Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1School of Women's and Infants' Health, The University of Western Australia, Perth, Western Australia.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  The genetic contribution of the NO system at the glutamatergic post-synapse to schizophrenia: Furthe...
Next Document:  An N-terminal pro-Atrial Natriuretic Peptide (NT-proANP) 'Aggregation-Prone' Segment Involved in Iso...