RT Journal Article
SR Electronic
T1 The effects of intra-nasally administered anti-inflammatory compounds in a mouse model of acute COPD exacerbations
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P672
VO 42
IS Suppl 57
A1 Vince Russell
A1 Andrew Connolly
A1 Joanna Dlugozima
A1 Paul Woodman
A1 Alan Young
YR 2013
UL http://erj.ersjournals.com/content/42/Suppl_57/P672.abstract
AB Exposure to tobacco smoke (TS) for 4d induced a steroid-insensitive lung inflammation in mice which was exaggerated by the addition of the viral mimetic poly IC (pIC). The effects of an inhaled steroid and an inhaled p38 inhibitor on the exaggerated inflammation were examined.Methods Mice were exposed to air or TS for 4d. Saline or pIC was administered intra-nasally and mice killed 24h after the last exposure, the lungs lavaged and cells counted. Single intra-nasal doses of vehicle, Fluticasone proprionate (FP, 0.3mg/kg) or the p38 inhibitor PF-03715455 (PF-55, 0.1mg/kg) were dosed 2h after the final challenge.Results TS-exposure caused a significant cellular infiltration into the lung, which was not inhibited by single doses of either PF-55 or FP. In non-TS exposed mice, pIC induced an inflammation which was also not inhibited by either PF-55 or FP. Administration of pIC in addition to TS-exposure induced an exaggerated inflammatory response which was greater than the additive effect of the two stimuli, with large increases in neutrophil numbers in particular (TS ∼0.07 million, PIC ∼0.2 million, TS+PIC ∼0.6 million). The inflammation at 24h after exposure was significantly inhibited by both PF-55 (54%, p<0.0001) and FP (44%, p<0.001), in contrast to the lack of efficacy of either compound in the TS or PIC groups. However, the level of inflammation never fell below the TS-alone baseline.Conclusions TS exposure for 4d induced a lung inflammation which was insensitive to steroid. Addition of PIC elicited a markedly enhanced inflammatory response that was sensitive to intra-nasal administration of PF-03715455 and also to FP, thus mimicking features of human COPD.