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The authors assessed the role of substance P (SP) and neurokinin A (NKA) and their receptor antagonists (RAs) SR140333 and SR48968 (respectively for NK(1) and NK(2) receptors) in pulmonary eosinophil influx induced by stimulation of capsaicin (CAP)-sensitive nerve terminals. The increase in respiratory system resistance after capsaicin infusion was attenuated by NK(2)RA and association of NK(1)NK(2)RA (P<.001). Respiratory system elastance (Ers) increase was attenuated with use of NK(1)NK(2)RA (P<.001). In alveolar wall, there was an increase in eosinophils after 30 minutes of CAP infusion (P<.001) and was attenuated after 24 hours. Pretreatment with NK(1)RA, NK(2)RA, and NK(1)NK(2)RA decreased eosinophils in alveolar wall (P<.001). SP induced an increase of eosinophils in alveolar wall (P<.001), although NKA may also contribute to this response. In airway wall, the authors observed an increase of eosinophils at 30 minutes (P=.006) till 24 hours after CAP infusion. They noticed a predominant influx of cells around airway wall after CAP and SP infusion. Pretreatment with NK(1)RA and NK(1)NK(2)RA reduced eosinophils (P<.001) in airway wall. Both SP and NKA contribute to eosinophil lung recruitment in distal airways and in alveolar wall, and these findings suggest that neurokinins may contribute to the development of eosinophilic inflammation in both allergic asthma and hypersensitivity pneumonitis.

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Background: Childhood bronchiolitis obliterans (CBO) is an infrequent but severe disease, characterized by persistent obstructive respiratory symptoms after an acute episode of bronchiolitis. Its etiology is mostly postviral, especially in developing countries. Pathologically, CBO is characterized as constrictive-type BO. The pathogenesis of this disease is poorly understood and there is no specific treatment. Animal models could help to better understand the sequence of events culminating in bronchiolar obliteration and serve as basis for experimental therapeutic research. Objectives: In this study, we adapted the nitric acid (NA) technique to develop a suitable model to study CBO in rats. Methods: We have intratracheally instilled 0.5% NA or saline and studied the histological lesions on days 2, 7, 14 and 30. NA-instilled animals developed a sequence of bronchiolar lesions that included necrotizing bronchiolitis, proliferative (PROL) bronchiolar lesions and constricitive (CONS) bronchiolar lesions with bronchiectasis, mucostasis and macrophagic accumulation. Results: The frequency of PROL lesions decreased and that of the CONS lesions increased, with a statistically significant difference at the sacrifice days, except for day 7 (PROL vs. CONS lesions day 2: p = 0.001; PROL vs. CONS lesions day 7: p = 0.38; PROL vs. CONS lesions day 14: p < 0.001; PROL vs. CONS lesions day 30: p < 0.001). Conclusions: We conclude that this model presents histological similarities with the histological picture of CBO, being suitable for further developmental and therapeutic experimental research in this field.

Our data reproduces, in mice, some of the features observed in melanoma patients treated with the combination of Mel and TNF-alpha. The identification of genes with altered expression by these drugs both individually and in combination might help in the understanding of their mechanism of action and, as a consequence, improved strategies that could impact their clinical application.