Privação de sono REM como fator de risco para o desenvolvimento de asma alérgica grave em modelo murino

• Ano de defesa: 2016
• Autor(a) principal: Oliveira Filho, Jethe Nunes de [UNIFESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Asthma; Asma
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=3836153; http://repositorio.unifesp.br/handle/11600/46268

Sleep quality influences a broad range of immune-mediated responses. Although different studies associated sleep deprivation with systemic inflammatory changes, the effect of sleep quality in the pathology of allergic diseases such as asthma is poorly understood. The aim of this work was to evaluate the influence of sleep deprivation on ovalbumin (OVA)-induced allergic inflammation in a murine model of asthma. OVA-sensitized mice were exposed to a first set of intranasal OVA challenge under sleep deprivation (SD) or healthy sleep (HS) condition followed by a second set of OVA challenge, one week apart. Some groups were subjected to corticoid treatment using dexamethasone. Bronchoalveolar lavage fluid (BALF), lungs, spleen and lymph nodes were collected and assessed for cellular content and cytokine production. Lung parenchyma histology performed to analyze inflammatory infiltration. OVA-sensitized SD mice developed a more severe airway inflammation than the HS group. Lung parenchyma revealed that the inflammation in SD mice was marked by the influx of neutrophils (mainly) and eosinophils and secretion of IL-6, TNF-?, and IL-17, in contrast to the classic eosinophilic inflammation and IL-4 production observed in allergic HS mice. The same cytokine profile was observed in ex vivo culture of lymph nodes cells and splenocytes, indicating that SD polarizes the immune responses in allergic mice towards a pro-Th17 profile. This idea is supported by the fact that disruption of IL-17 signaling (IL-17RA-/-) prevented the airway neutrophilia in allergic SD mice. Furthermore, SD allergic mice became refractory to corticoid treatment, in contrast to HS group.