Role of the tachykinin NK1 receptor in a murine model of cigarette smoke-induced pulmonary inflammation

<p>Abstract</p> <p>Background</p> <p>The tachykinins, substance P and neurokinin A, present in sensory nerves and inflammatory cells such as macrophages and dendritic cells, are considered as pro-inflammatory agents. Inflammation of the airways and lung parenchyma plays a major role in the pathogenesis of chronic obstructive pulmonary disease (COPD) and increased tachykinin levels are recovered from the airways of COPD patients. The aim of our study was to clarify the involvement of the tachykinin NK₁receptor, the preferential receptor for substance P, in cigarette smoke (CS)-induced pulmonary inflammation and emphysema in a mouse model of COPD.</p> <p>Methods</p> <p>Tachykinin NK₁receptor knockout (NK₁-R^-/-) mice and their wild type controls (all in a mixed 129/sv-C57BL/6 background) were subjected to sub acute (4 weeks) or chronic (24 weeks) exposure to air or CS. 24 hours after the last exposure, pulmonary inflammation and development of emphysema were evaluated.</p> <p>Results</p> <p>Sub acute and chronic exposure to CS resulted in a substantial accumulation of inflammatory cells in the airways of both WT and NK₁-R^-/-mice. However, the CS-induced increase in macrophages and dendritic cells was significantly impaired in NK₁-R^-/-mice, compared to WT controls, and correlated with an attenuated release of MIP-3α/CCL20 and TGF-β1. Chronic exposure to CS resulted in development of pulmonary emphysema in WT mice. NK₁-R^-/-mice showed already enlarged airspaces upon air-exposure. Upon CS-exposure, the NK₁-R^-/-mice did not develop additional destruction of the lung parenchyma. Moreover, an impaired production of MMP-12 by alveolar macrophages upon CS-exposure was observed in these KO mice. In a pharmacological validation experiment using the NK₁receptor antagonist RP 67580, we confirmed the protective effect of absence of the NK₁receptor on CS-induced pulmonary inflammation.</p> <p>Conclusion</p> <p>These data suggest that the tachykinin NK₁receptor is involved in the accumulation of macrophages and dendritic cells in the airways upon CS-exposure and in the development of smoking-induced emphysema. As both inflammation of the airways and parenchymal destruction are important characteristics of COPD, these findings may have implications in the future treatment of this devastating disease.</p

Efeito da radioterapia na função pulmonar e na fadiga de mulheres em tratamento para o câncer de mama

O presente estudo comparou a função pulmonar e a fadiga de mulheres antes e após a radioterapia (RT) adjuvante para tratamento do câncer de mama, e correlacionou a função pulmonar com a dose de radiação e fadiga. Foi conduzido um estudo observacional longitudinal envolvendo 20 mulheres. A função pulmonar foi avaliada pela espirometria (ClementClarke®) e manovacuometria (GlobalMed®, modelo MVD 300), e a fadiga pelo Functional Assessment of Cancer Therapy Fatigue (FACT-F). Todas as avaliações foram realizadas antes da primeira sessão e uma semana após o término da RT adjuvante. Para a análise estatística foram utilizados os testes Wilcoxon Signed Rank Test e correlação de Spearman, adotando-se nível de significância p<0,05. Na espirometria, encontrou-se redução significativa da capacidade vital forçada (23,52%), do volume expiratório forçado no primeiro segundo (26,23%) e do pico de fluxo expiratório (10,12%) (p=0,001). As pressões expiratórias e inspiratórias máximas também diminuíram significativamente (25,45 e 32,92%, respectivamente). Observou-se diminuição significativa do bem-estar físico e do bem-estar funcional, e um aumento significativo da fadiga no FACT-F (p=0,001). Não foram observadas correlações entre as variáveis da função pulmonar com a dose de radiação e fadiga. Em curto prazo, a RT promoveu redução na função pulmonar, mas a mesma permaneceu próxima à normalidade para a amostra estudada. Observou-se aumento significativo da fadiga e diminuição dos escores dos domínios bem-estar físico e funcional