Imperial College London
Portrait Picture

DR COEN WIEGMAN

Faculty of Medicine, National Heart & Lung Institute

Senior Teaching Fellow
 
 
 
//

Contact

 

+44 (0)20 7594 1980c.wiegman

 
 
//

Location

 

305Guy Scadding BuildingRoyal Brompton Campus

//

Summary

 

Publications

Citation

BibTex format

@inproceedings{Wiegman:2015:10.1089/jamp.2015.ab01.abstracts,
author = {Wiegman, CH and Adcock, IM and Rothaul, A and Main, M and Morgan, F},
doi = {10.1089/jamp.2015.ab01.abstracts},
pages = {A23--A23},
publisher = {Mary Ann Liebert},
title = {ACTIVITY OF THE NOVEL AND SELECTIVE PANJANUS KINASE (JAK) INHIBITOR VR588 IN A MURINE POLYINOSINIC: POLYCYTIDILIC ACID (POLY(I:C)) MODEL OF VIRAL LUNG INFLAMMATION},
url = {http://dx.doi.org/10.1089/jamp.2015.ab01.abstracts},
year = {2015}
}
Download

RIS format (EndNote, RefMan)

TY  - CPAPER
AB  - Rationale: VR588 is a potent, selective pan-JAK inhibitor. Viralinfection is regarded as an important trigger of airway inflammation.This study investigates VR588 by the inhaled and oral routes in amurine model of viral lung inflammationMethods: Male BALB/c mice were administered Poly(I:C) 1 mg/mlintranasally (i.n) 1 hour after VR588 administration and again 16 hourslater. VR588 was given (i.n 1.5, 7.5, 15 mg/kg and p.o 15 mg/kg; n¼6per group). Lung tissue and bronchoalveolar lavage fluid (BALF) washarvested 40 hours after the initial Poly(I:C) challenge. Inflammatorycell count from BALF (FACS analysis), JAK-STAT activation(pSTAT1, 3 & 5) (ELISA) and BAL inflammatory cytokines (Lumineximmunoassay) were measured. Fluticasone propionate (FP) (i.n 1.5 mg/kg) and tofacitinib (T) (p.o 15 mg/kg) were positive controls.Results: Poly(I:C) increased total BAL cell count which was reducedin a dose-related manner by i.n VR588; oral VR588 was ineffective. Poly(I:C)-elevated BAL cytokines (eotaxin, MIP-1a & b, IP-10, KC, TNF-aand MCP-1) were all reduced by i.n VR588. pSTAT1 and pSTAT5 (butnot pSTAT3) were increased by Poly(I:C) and subsequently attenuatedby VR588. Intranasal VR588 activity was typically greater than that seenfor oral and at least as great as that with FP or T.Conclusions: VR588 attenuation of Poly(I:C) induced inflammatorycell accumulation, cytokines and STAT phosphorylation supportsits possible use in the treatment of viral induced airway inflammation.
AU  - Wiegman,CH
AU  - Adcock,IM
AU  - Rothaul,A
AU  - Main,M
AU  - Morgan,F
DO  - 10.1089/jamp.2015.ab01.abstracts
EP  - 23
PB  - Mary Ann Liebert
PY  - 2015///
SN  - 1941-2711
SP  - 23
TI  - ACTIVITY OF THE NOVEL AND SELECTIVE PANJANUS KINASE (JAK) INHIBITOR VR588 IN A MURINE POLYINOSINIC: POLYCYTIDILIC ACID (POLY(I:C)) MODEL OF VIRAL LUNG INFLAMMATION
UR  - http://dx.doi.org/10.1089/jamp.2015.ab01.abstracts
UR  - http://hdl.handle.net/10044/1/29985
ER  -
Download