TY - JOUR T1 - Poly I:C treatment causes fatal AHR in sensitized mice JF - European Respiratory Journal JO - Eur Respir J VL - 38 IS - Suppl 55 SP - p966 AU - M. Starkhammar AU - S. Georen-Kumlien AU - S.-E. Dahlén AU - M. Adner AU - L.-O. Cardell Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/p966.abstract N2 - Respiratory infections are known to promote airway hyperresponsiveness (AHR) in asthmatic patients. Toll-like receptors (TLRs) are parts of the innate immune system that recognize viral and bacterial components. This in vivo study explores the relation between TLR activation and AHR in a model of allergic airway inflammation.Female BALB/c mice where sensitized on day 1 and 8, then challenged with either ovalbumin (OVA) or PBS on day 15-17. PolyI:C activating TLR3, LPS triggering TLR4 or PBS were then given i.n. during 4 consecutive days. On day 22 the outcome of metacholine (Mch) induced airway resistance was investigated with flexiVent® technique. Cells and inflammatory mediators were analysed in bronchoalveolar fluid (BALF).PolyI:C and LPS treated mice developed a marked AHR not seen among control mice. The airway resistance reached critically high levels in mice concomitantly challenged with OVA (Rmax at 1mgMch/kg: PBS: 2.1±0.1, PBS-LPS: 2.9±0.3, PBS-polyI:C: 3.6±0.2, OVA:5.6±0.2, OVA-LPS: 9.3±0.6 and OVA-polyI:C: 7.3±0.5 cmH2O s ml-1). The OVA-polyI:C mice also displayed circulatory collapse (p<0.05). PolyI:C increased the amount of lymphocytes and LPS neutrophils in BALF. Multivariate analysis of a panel of inflammatory mediators could not reveal a clear separation between PBS and OVA groups. However, polyI:C treatment induced a specific increase of IL-12 and KC in both treatment groups.Costimulation with PolyI:C and LPS, representing viral and bacterial activation, respectively, caused AHR above the effect of OVA which in by polyI:C caused fatal circulatory responses. It is therefore tempting to suggest that TLRs might play a vital role in virus-induced exacerbation of allergic asthma. ER -