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Notes: Background Respiratory syncytial virus (RSV) infection is known to develop and exacerbate asthma in young children. In adult, RSV causes recurrent but asymptomatic infections. However, the impact of asymptomatic RSV infection on adult asthma is yet to be determined. The present study is designed to determine the effects of primary and secondary low-grade RSV infections on allergic airway inflammation in a murine model of allergic asthma.Methods A low-grade RSV (2 × 103 plaque-forming units/mouse) was inoculated, and this caused neither pulmonary inflammation nor symptoms but induced significant IFN-γ production in thoracic lymph nodes. To investigate interaction between low-grade virus and Dermatophagoides farinae (Df), airway hyper-responsiveness, lung inflammation and cytokine production from thoracic lymph nodes were compared after primary and secondary low-grade RSV infections in four groups of mice; control, Df allergen-sensitized, RSV-infected and Df-sensitized RSV-infected mice. A direct comparison between low- and high-grade RSV infections was also performed in primary infection. To investigate the role of IL-5 during secondary RSV infection, anti-IL-5 monoclonal antibody (anti-IL-5 mAb) was injected in mice and similar parameters were compared in four groups of mice.Results Primary high-grade RSV infection increased allergen-induced airway inflammation, while primary low-grade RSV infection attenuated allergen-induced airway inflammation concomitant with significant IFN-γ production in lung-draining lymph nodes. In marked contrast, secondary low-grade RSV infection increased both IFN-γ and IL-5 production, resulting in exacerbation of allergen-induced airway inflammation. Anti-IL-5 mAb treatment in secondary low-grade RSV infection and Df allergen-sensitized mice attenuated virus and allergen-induced airway inflammation.Conclusions Low-grade RSV infection per se does not cause pulmonary inflammation, whereas it induces a significant immunological response in the allergen-sensitized host. These results indicate that subclinical and recurrent RSV infection may play an important role in exacerbation and maintenance of asthma in adults, wherein IL-5 is critically involved.

Notes: Background The cysteinyl leukotriene receptor 1 (cysLTR1) antagonists are useful for oral treatment of bronchial asthma. The underlying mechanism of cysLTR1 antagonists on inhibition of inflammatory cytokine production is yet to be determined.Objective The present study was designed to determine the effect of pranlukast, a cysLTR1 antagonist, on production of inflammatory cytokines by allergen-stimulated peripheral blood monocytes (PBM) from atopic asthmatics.Methods PBM were obtained from normal control (n = 10) and Dermatophagoides farinae (Der f) allergen-sensitized atopic asthmatics (n = 12), and were cultured in the presence of Der f allergen. The production of TNF-α and nuclear-translocation of nuclear factor kappa B (NF-κB) was determined. In atopic asthmatics, pranlukast, tacrolimus or dexamethasone was added before stimulation by Der f. The additive effect of pranlukast and dexamethasone was also determined.Results PBM from atopic asthmatics cultured with Der f exhibited a significant increase in TNF-α production and nuclear translocation of NF-κB compared with normal control (P 〈 0.01). Pranlukast, tacrolimus and dexamethasone significantly inhibited production of TNF-α and nuclear-translocation of NF-κB in PBM of atopic asthmatics (P 〈 0.01). An additive effect of pranlukast on low-dose dexamethasone was also demonstrated. However, LTD4 did not induce TNF-α production or NF-κB nuclear translocation.Conclusion Our results suggest that pranlukast may inhibit TNF-α production via suppression of NF-κB activation through pathways distinct from cysLTR1 antagonism.

Notes: Background Dendritic cells (DCs) play an important role in the immune response and are critically involved in asthma. β2-agonists could potentially exacerbate type 2 T helper (Th2) cell-mediated immune response.Objectives To determine the effects of various anti-asthmatic agents on DCs function both in vitro and in vivo.Methods Murine bone marrow-derived DCs were pulsed with mite allergen in the presence of pranlukast, salbutamol, salmeterol or fluticasone. These DCs were then inoculated intranasally into naïve mice to induce allergic airway inflammation in vivo.Results Pranlukast reduced IL-10 and increased IL-12, while fluticasone reduced both IL-10 and IL-12 production by mite allergen-pulsed DCs. Allergic airway inflammation in pranlukast- and fluticasone-treated and mite allergen pulsed DCs-harbouring mice was attenuated and such response was associated with inhibition of Th2 response in the airway. Salbutamol did not alter cytokine production, while salmeterol reduced IL-12 production by mite allergen-pulsed DCs. Lung pathology in β2-agonist-harbouring mice was comparable with those of mite allergen-pulsed DCs-harbouring mice.Conclusions Our results indicate that leukotriene receptor antagonists and corticosteroids inhibit DCs-induced Th2 skewed immune response, and that short- and long-acting β2-agonists do not modify DCs-induced allergic airway inflammation.

Notes: Background:  About 70% of childhood asthmatics become free of asthma-related symptoms during adolescence. Little is known about bronchial hyperresponsiveness (BHR) and airway inflammation in young adults with “outgrown” childhood asthma.Methods:  We studied 61 nonsmoking medical students (18 intermittent mild asthmatics, 23 students with outgrown childhood asthma but free of asthma-related symptoms for 10 years (asymptomatic asthmatics) and 20 healthy students). BHR and lung function were measured, and induced sputum samples analyzed for eosinophil count, eosinophilic cationic protein (ECP), granulocyte-macrophage colony stimulating factor (GM-CSF), and tumor necrosis factor-α (TNF-α).Results:  BHR was still present in most asymptomatic asthmatics, but it was milder compared with healthy students. Only three subjects with previous asthma had no BHR and no signs of airway inflammation. Percentages of eosinophil, and ECP, TNF-α and GM-CSF concentrations in induced sputum of mild asthmatics and asymptomatic asthma groups were higher than in the healthy group. In asymptomatic asthmatics group, the duration of asthma, sputum eosinophil percentage, and the level of TNF-α in sputum correlated significantly with BHR.Conclusions:  Only a few subjects with longstanding asymptomatic asthma could be considered as cured; most asymptomatic asthmatics continued to exhibit BHR and signs of airway inflammation. The outcome of childhood asthma and BHR was associated with the degree of airway inflammation and the duration of childhood asthma.