Abstract
We recently described a new model to study non-invasively with magnetic resonance imaging (MRI) the effects of compounds to prevent and/or resolve airway inflammation induced by ovalbumin in the lungs of actively sensitised rats. We report here the effects of 4-(4-fluorophenyl)-2-(1-methylpiperidin-4-yl)-5-(2-(1-( S)-phenylethyl)amino-4-pyridinyl)thiazole fumarate (Compound 1), which exhibits inhibitory activity against p38α and p38β2 and residual activity on c- Jun amino-terminal kinase (JNK)2 mitogen-activated protein (MAP) kinases, on the oedematous signals detected by MRI and generated by antigen challenge in the lungs of sensitized rats. Compound 1 (10 mg kg −1) given orally 1 h prior to allergen challenge significantly reduced the oedematous signal measured at 24 h. Similar effects were seen with a synthetic corticosteroid, mometasone furoate (0.3 mg kg −1), given intratracheally 3 h prior to challenge. For both compounds, inhibition of the oedematous signal was accompanied by reductions in the inflammatory parameters in the bronchoalveolar lavage fluid measured 24 h after challenge with ovalbumin. Compound 1 (10 mg kg −1) administered 24 h after challenge with ovalbumin did not change the rate of resolution of the signal detected by MRI in the lungs. In contrast, mometasone furoate (0.3 mg kg −1) significantly increased resolution of these signals, which was evident 3 h after drug administration and maintained to 48 h post challenge. Collectively, our data suggest that the p38 MAP kinase inhibitor Compound 1 shows a different profile than glucocorticosteroids since its ability to resolve existing inflammation is limited.
Published Version
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