RT Journal Article
SR Electronic
T1 An anti-human ICAM-1 antibody inhibits human rhinovirus infection in the mouse model of human major group rhinovirus infection
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP p3501
VO 38
IS Suppl 55
A1 Stephanie Traub
A1 Alan Carruthers
A1 Rebecca Dunmore
A1 Leila Gogsadze
A1 Nathan W. Bartlett
A1 Weidong Hao
A1 Qing Zhu
A1 Katie Bernard
A1 Michael Dymond
A1 Andrew Leishman
A1 Alison Humbles
A1 Ian K. Anderson
A1 Roland Kolbeck
A1 Matthew Sleeman
A1 Ted Wells
A1 Sebastian L. Johnston
YR 2011
UL http://erj.ersjournals.com/content/38/Suppl_55/p3501.abstract
AB Introduction: Human rhinoviruses (HRV) cause the common cold and the majority of acute exacerbations of asthma and COPD. 90% of HRV belong to the major group and use human ICAM-1 (intercellular adhesion molecule 1) for cell attachment and entry. We previously established a human/mouse chimeric ICAM-1 transgenic mouse model of human major group rhinovirus infection. However, antiviral approaches have not yet been studied in this model.Aim: To evaluate the inhibition of HRV-induced airway inflammation by a mouse anti-human ICAM-1 antibody.Methods: Transgenic mice were treated i.n. or i.v. with an ICAM-1 antibody before HRV16 or HRV14 challenge. To exclude possible effects of an ICAM-1 antibody on cell trafficking we evaluated an ICAM-1 antibody in the transgenic mice by infecting them with minor group HRV1B or in an LPS challenge model.Results: Both i.n. and i.v. dosed ICAM-1 antibody inhibited HRV16 induced bronchoalveolar lavage (BAL) cells (p&lt;0.001 and p&lt;0.001, respectively), lymphocytes (p&lt;0.001 and p&lt;0.01), neutrophils (p&lt;0.001 and p&lt;0.001) and macrophages (p&lt;0.01 and p=ns). Intranasal administered ICAM-1 antibody reduced HRV16 induced IL-1β (p&lt;0.001), IL-6 (p&lt;0.001) and IFNλ2/3 (p&lt;0.01) as well as ITAC (p&lt;0.001), IP-10 (p&lt;0.001) and KC (p&lt;0.001) in BAL. Similar data were observed with ICAM-1 antibody and HRV14 infection. Control experiments with minor group HRV1B as well as in an LPS challenge model showed no effect of ICAM-1 antibody on either HRV1B- or LPS-induced airway inflammation (p=ns for all outcomes).Conclusion: We have shown for the first time that an anti-human ICAM-1 specific antibody can be used to prevent human rhinovirus entry and replication and induction of airway inflammation in vivo.