TY - JOUR 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 VL - 38 IS - Suppl 55 SP - p3501 AU - Stephanie Traub AU - Alan Carruthers AU - Rebecca Dunmore AU - Leila Gogsadze AU - Nathan W. Bartlett AU - Weidong Hao AU - Qing Zhu AU - Katie Bernard AU - Michael Dymond AU - Andrew Leishman AU - Alison Humbles AU - Ian K. Anderson AU - Roland Kolbeck AU - Matthew Sleeman AU - Ted Wells AU - Sebastian L. Johnston Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/p3501.abstract N2 - 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<0.001 and p<0.001, respectively), lymphocytes (p<0.001 and p<0.01), neutrophils (p<0.001 and p<0.001) and macrophages (p<0.01 and p=ns). Intranasal administered ICAM-1 antibody reduced HRV16 induced IL-1β (p<0.001), IL-6 (p<0.001) and IFNλ2/3 (p<0.01) as well as ITAC (p<0.001), IP-10 (p<0.001) and KC (p<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. ER -