RESUMO
BACKGROUND: IL-25, a novel member of the IL-17 cytokine family, promotes CD4+ T-helper 2 lymphocyte-like (Th type-2) inflammatory responses in the lung. Although IL-25 up-regulates IL-13 in the lung, the contribution of this and other type 2 cytokine signalling pathways to the induction and persistence of airways hyper-reactivity (AHR) and allergic inflammation are unclear. OBJECTIVE: To determine the downstream factors employed by IL-25 to induce Th type-2 pulmonary inflammation and AHR. METHODS: IL-25 was delivered to the airways of BALB/c mice by intra-tracheal (i.t.) instillation and AHR and Th type-2 inflammatory responses were characterized in wild type (WT) and Th type-2-cytokine and -signalling pathway-deficient (-/-) mice. RESULTS: IL-25 treatment resulted in AHR, eosinophilic inflammation, mucus hypersecretion and a progressive increase in the production of Th type-2 cytokines in the lungs. Levels of arginase-I (arg-I) and eotaxin were also elevated by IL-25 treatment. A significant reduction in AHR, and attenuation of mucus production was observed in IL-25-treated IL-13-/-, IL-4 receptor alpha (IL-4Ralpha-/-)- and signal-transducer-and-activator-of-transcription-factor-6 (STAT6-/-)-deficient mice. AHR was also inhibited in IL-4(-/-)- and IL-5/eotaxin(1)(-/-)- deficient mice treated with IL-25, however, mucus hypersecretion was not completely ablated. IL-25 promoted Th type-2 responses by directly acting on naïve T cells. CONCLUSION: IL-25 potently (single dose) induces sustained AHR and acute pulmonary inflammation with eosinophilia. IL-25-induced AHR is dependent on the production of Th type-2 cytokines, and removal of IL-13 and its signal transduction pathway prevents IL-25-induced airways inflammation and AHR. IL-25 potently induces inflammatory cascades that may exacerbate allergic airways inflammation by promoting Th type-2 cytokine responses in conjunction with the up-regulation of factors (eotaxin and arg-I) that can amplify inflammation associated with allergic disorders. Dysregulation in IL-25 production may predispose to features of allergic airways disease.
Assuntos
Citocinas/imunologia , Interleucina-17/farmacologia , Pulmão/imunologia , Pneumonia/imunologia , Células Th2/imunologia , Animais , Arginase/análise , Arginase/genética , Asma/imunologia , Biomarcadores/análise , Hiper-Reatividade Brônquica/imunologia , Testes de Provocação Brônquica , Células Cultivadas , Quimiocina CCL11 , Quimiocinas CC/análise , Quimiocinas CC/genética , Citocinas/genética , Interleucina-13/genética , Interleucina-13/imunologia , Interleucina-17/imunologia , Interleucina-4/genética , Interleucina-4/imunologia , Pulmão/patologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Muco/metabolismo , Pneumonia/patologia , RNA Mensageiro/análise , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/imunologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Transcrição STAT6/genética , Fator de Transcrição STAT6/imunologia , Transdução de Sinais/fisiologiaRESUMO
Post-mortem examinations of 236 goats from all provinces in Mongolia were performed for the study of helminths in goats. Thirty-nine helminth species belonging to three classes, 14 families and 23 genera were found. Trichocephalus spiralis and Avitellina centripunctata are reported for the first time in goats in Mongolia. The prevalence and intensity of helminth infections are reported for three age groups of goats in four seasons and three geographic zones in Mongolia. Common helminth infections of goats in all zones of Mongolia were infections of Ostertagia, Marshallagia and Nematodirus. In addition, fecal samples of 15 kids, 15 yearlings and 15 adult goats were examined monthly for eggs. The highest number of eggs per gram (EPG) of feces was counted in March (average 1335.3+/-405.3) and the lowest count was in November (54+/-18.6).
