, 1997 and Gauvreau et al., 2011). There are also recent suggestions

that central reflexes may drive a LAR in some models of allergen challenge in guinea-pigs (Smit et al., 2014). Functional responses to allergens demonstrate low intra-subject but high inter-subject variation in humans (Kopferschmitt-Kubler et al., 1987). The reasons for this variability are likely to be multifactorial including gender and total and allergen-specific IgE levels (Petersen, Mosbech, & Skov, 1996). Examination of the individual guinea-pig responses in the final protocol of the present study highlights how this phenomenon is also observed in animal models. This emphasises the need for including sufficient numbers in experimental groups to have sufficient statistical power, as well as multiple measurements to SCH772984 evaluate peak responses over a wide temporal window. In conclusion, this study has demonstrated a dissociation between eosinophil influx and LAR as well as AHR. It has highlighted that assessing RG7204 in vitro parameters in isolation, such as inflammatory cell influx

in bronchoalveolar lavage fluid, would fail to identify if other key components of the allergic response and its functional outcomes (e.g. AHR) are absent. These models would be inadequate for examining the complex relationship between inflammatory and functional parameters that would be required in preclinical testing of novel therapeutics or identification of potential therapeutic mechanisms. Finally, we achieved our objective of restoring a full profile of functional and inflammatory responses by manipulating the sensitisation and challenge protocols. An equal contribution to the original idea, study design, analysis and preparation by Alexander Lowe, Anthony Nials, William Ford, Isotretinoin Emma

Kidd and Kenneth Broadley. The experimental contribution was made by Alexander Lowe. This study was supported by a Medical Research Council (MRC-CASE G0900180), UK/GlaxoSmithKline CASE studentship to Alexander Lowe. We thank Christie James for assisting in the processing of histology samples. “
“Dose–response studies typically produce data that manifest as a sigmoid curve when a response is plotted against dosage (Fig. 1). A common inference done from such a curve is the estimation of the dose at which 50% of the subjects show the desired response. This is usually done by means of the four-parameter logistic nonlinear regression model (Eq. 1), modified from the original equation developed by A.V.