Allergic airway disease is unaffected by the absence of IL-4Rα-dependent alternatively activated macrophages.

BACKGROUND: Markers of alternatively activated macrophages (AAMs) are upregulated in the lungs of asthmatic patients and in mice with allergic airway disease. AAMs are thought to contribute to the pathogenesis of allergic airway disease by virtue of their decreased NO production and increased production of proline and polyamines, which are important in the synthesis of connective tissues such as collagen. OBJECTIVE: We aimed to define the role of AAMs in the pathogenesis of allergic airway disease. METHODS: The IL-4 receptor alpha (IL-4Rα) gene is genetically abrogated in macrophages in LysM(cre)IL-4Rα(-/lox) mice, which therefore have impaired IL-4/IL-13 activation of AAMs through IL-4R types 1 and 2. Responses of LysM(cre)IL-4Rα(-/lox) mice and IL-4Rα(-/lox) littermate controls were examined in ovalbumin- and house dust mite-induced allergic airway disease. RESULTS: IL-4Rα expression was shown to be efficiently depleted from alveolar macrophages, interstitial macrophages, and CD11b(+)MHCII(+) inflammatory macrophages. Although the expression of markers of AAMs such as Ym-1, arginase and found in inflammatory zone 1 was decreased in macrophages of LysM(cre)IL-4Rα(-/lox) mice in chronic ovalbumin-induced allergic airway disease, airway hyperreactivity, T(H)2 responses, mucus hypersecretion, eosinophil infiltration, and collagen deposition were not significantly reduced. LysM(cre)IL-4Rα(-/lox) mice and littermate controls also developed similar responses in acute ovalbumin- and house dust mite-induced allergic airway disease. CONCLUSION: Our results suggest that the presence of AAMs in allergic airway disease may be only an association, as a result of the increased T(H)2 responses present during disease, and that IL-4Rα-dependent AAMs do not play an important role in the pathology of disease.

Investigation of in vitro and in vivo anti-asthmatic properties of Siphonochilus aethiopicus.

AIM OF THE STUDY: Asthma is a chronic inflammatory disease of the lungs, characterized by increased sensitivity to bronchoconstriction associated with infiltration of immune cells, mucus hypersecretion and structural remodelling of the airways. In South Africa, the indigenous plant Siphonochilus aethiopicus, is used by traditional health practitioners to treat colds, wheezing of the chest, coughs, influenza, sinus problems and mild asthma. In this study we aimed to investigate the potential anti-inflammatory and anti-allergic properties of S. aethiopicus in vitro and its efficacy in a mouse model of allergic asthma. MATERIALS AND METHODS: The dried and powdered S. aethiopicus plant material was extracted separately with organic solvents (diethyl ether, ethanol) and water. Dried extracts as well as a purified furanoterpenoid compound present in the extracts were screened in vitro in a glucocorticoid and histamine H(1) receptor binding assay and a phosphodiesterase IV enzyme inhibition assay. Extracts were also evaluated for efficacy against ovalbumin (OVA)-induced allergic airway disease in mice. RESULTS: Biological assaying of extracts of the plant and the isolated furanoterpenoid showed significant in vitro inhibition of glucocorticoid and histamine H(1) receptor binding and phosphodiesterase IV activity, supporting a possible anti-inflammatory, anti-allergic and bronchodilatory effect. Administration of S. aethiopicus extracts to OVA-sensitized and challenged mice significantly reduced lung inflammation and the percentage of eosinophils in bronchoalveolar lavage fluid but did not influence airway hyperreactivity. CONCLUSION: This study provides evidence that S. aethiopicus has anti-inflammatory and anti-allergic properties in vitro and in vivo. These findings may support anecdotal accounts of its effectiveness against asthma, sinusitis, colds and flu.