BackgroundAsthma is an inflammatory condition characterized by airway hyperresponsiveness and chronic inflammation. The resolution of inflammation is an essential process to treat this condition. In this study we investigated the effect of Allium cepa L. extract (AcE) and quercetin (Qt) on cytokine and on smooth muscle contraction in vitro and its therapeutic potential in a murine model of asthma.MethodsAcE was obtained by maceration of Allium cepa L. and it was standardized in terms of quercetin concentration using high performance liquid chromatography (HPLC). In vitro, using AcE 10, 100 or 1000 μg/ml or Qt 3.5, 7.5, 15 μg/ml, we measured the concentration of cytokines in spleen cell culture supernatants, and the ability to relax tracheal smooth muscle from A/J mice. In vivo, Blomia tropicalis (BT)-sensitized A/J mice were treated with AcE 100, 1000 mg/kg or 30 mg/kg Qt. We measured cell influx in bronchoalveolar lavage (BAL), eosinophil peroxidase (EPO) in lungs, serum levels of Bt-specific IgE, cytokines levels in BAL, and lung histology.ResultsWe observed a reduction in the production of inflammatory cytokines, a relaxation of tracheal rings, and a reduction in total number of cells in BAL and EPO in lungs by treatment with AcE or Qt.ConclusionAcE and Qt have potential as antiasthmatic drugs, as they possess both immunomodulatory and bronchodilatory properties.

Allergic asthma has emerged as an important public health problem of urban populations in developed countries. Very often herbal medicine is used to treat this widespread disease, due to the lack of efficacy and the important side effects related to the classical drugs in use. Along this line, Ocimum gratissimum (Og) is a plant widely used in Brazilian folk medicine to treat inflammatory disorders, such as asthma. In the present study we evaluated the immunomodulatory effects of Og and rosmarinic acid (RA, a polyphenolic compound) in a murine model of respiratory allergy induced by the Blomia tropicalis (Bt) mite. The respiratory allergy was induced in A/J mice by administration of Bt extract and the treatment was done using 25, 50 or 100mg/kg of an Og methanolic extract or using 2, 20 or 200mg/kg of RA. We then evaluated the changes induced by these drugs on immunological parameters related to the allergic process, which are up-regulated in this allergic model. The treatment of animals with 100mg/Kg Og and 200mg/Kg RA led to a significant reduction in the numbers of leukocytes/eosinophils in bronchoalveolar lavage (BAL); eosinophil peroxidase activity in BAL; presence of mucus in respiratory tract, histopathological changes in the lung, and IL-4 in BAL. These results suggest that the methanolic extract of Og and the polyphenol RA have therapeutic potential in this murine model of respiratory allergy to a clinically relevant human sensitizer allergen.

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Background Most studies assessing pathophysiological heterogeneity in asthma have been conducted in high-income countries (HICs), with little known about the prevalence and characteristics of different asthma inflammatory phenotypes in low-and middle-income countries (LMICs). This study assessed sputum inflammatory phenotypes in five centres, in Brazil, Ecuador, Uganda, New Zealand (NZ) and the United Kingdom (UK). Methods We conducted a cross-sectional study of 998 asthmatics and 356 non-asthmatics in 2016–20. All centres studied children and adolescents (age range 8–20 years), except the UK centre which involved 26–27 year-olds. Information was collected using questionnaires, clinical characterization, blood and induced sputum. Results Of 623 asthmatics with sputum results, 39% (243) were classified as eosinophilic or mixed granulocytic, i.e. eosinophilic asthma (EA). Adjusted for age and sex, with NZ as baseline, the UK showed similar odds of EA (odds ratio 1.04, 95% confidence interval 0.37–2.94) with lower odds in the LMICs: Brazil (0.73, 0.42–1.27), Ecuador (0.40, 0.24–0.66) and Uganda (0.62, 0.37–1.04). Despite the low prevalence of neutrophilic asthma in most centres, sputum neutrophilia was increased in asthmatics and non-asthmatics in Uganda. Conclusions This is the first time that sputum induction has been used to compare asthma inflammatory phenotypes in HICs and LMICs. Most cases were non-eosinophilic, including in settings where corticosteroid use was low. A lower prevalence of EA was observed in the LMICs than in the HICs. This has major implications for asthma prevention and management, and suggests that novel prevention strategies and therapies specifically targeting non-eosinophilic asthma are required globally.

Medicinal plants have long been used as an alternative to traditional drugs for the treatment of inflammatory conditions due to the classical side effects and restricted access of various commercially available drugs, such as steroids (GCs) and nonsteroidal anti-inflammatory drugs (NSAIDs). Sambucus australis is a Brazilian herb that is commonly used to treat inflammatory diseases; however, few studies have examined the use of this species in the treatment of inflammatory conditions. The present study aims to evaluate the potential anti-inflammatory activity of S. australis in vitro. We established spleen cell cultures stimulated with pokeweed mitogen (PWM) to evaluate the production of proinflammatory cytokines, such as Il-4, Il-5, IFN-y, and Il-10 (by elISA), and the expression of the transcription factor NF-kB (by RT-PCR). In addition, we evaluated the levels of nitric oxide in macrophage cultures and the membranestabilizing activity of S. australis methanolic extract (eMSA). Treatment with eMSA at concentrations of 100, 50, 25 and 12.5 µg/ml significantly decreased IL-4 (p<0.001) and IL-5 (p<0.001) levels. Treatment with 100 µg/ml EMSA reduced IFN-у (p<0.001) levels. Moreover, at 100 mg/ml, EMSA also increased IL-10 production and reduced NF-kB expression (p<0.01). In macrophage cultures stimulated with LPS, EMSA decreased nitric oxide levels (p<0.001) at all concentrations tested (100, 50, 25 and 12.5 µg/ ml). Additionally, EMSA had a protective effect in the erythrocyte membrane stabilization assay. Taken together, these results suggest that S. australis has anti-inflammatory potential in vitro, characterized by the reduction of both inflammatory cytokines and the expression of NF-kB along with the up-regulation of Il-10.

RATIONALE: Aryl hydrocarbon receptor (AhR), a receptor for common environmental contaminants, is an important regulator of immune responses. Our previous studies have suggested a role of AhR in protecting against cockroach allergen-induced lung inflammation by using AhR-/mice. Autophagy plays a major role in controlling immune responses and inflammation. We sought to determine whether the activated AhR signaling specifically in airway epithelium by cockroach allergen modulates cockroach allergen-induced lung inflammation through autophagy METHODS: The role of AhR expressed in epithelium in cockroach allergen (CRE) induced allergic inflammation was investigated in a mouse model of asthma with AhR epithelial conditional knock out mice (ftpc-Cre;AhR flox/flox). Cockroach allergen induced the activation of AhR and autophagy signaling in epithelium was determined. The role of autophagy in CRE-induced asthma was also investigated. RESULTS: CRE-challenged Sftpc-Cre; AhR flox/flox mice displayed decreased lung infiltrates, mucus production, and airway hyper-responsiveness. These mice also showed reduced levels of IL-4, IL-5, IL-13, IL-17, but increased IL-10 and IL-22 in the BAL fluids. Decreased IC3B II in airways was also observed. Moreover, CRE can activate AhR (CYP1A1 and CYP1B1) and autophagy (Beclin-1, Atg5, and p62) signaling in epithelial cells in vitro, and AhR agonist TCDD can potentiate CRE-induced autophagy. Furthermore, CRE-induced lung inflammation was significantly suppressed when autophagy inhibitor was used in the mouse model with decreased lung infiltrates and Th2/T17 cytokines in BAL fluids. CONCLUSIONS: Contrast to the protective role previously observed in AhR-/mice, AhR in airway epithelial may exacerbate CRE-induced inflammation, which may through activating autophagy signaling.

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RATIONALE: Cytomegalovirus (CMV) is a recognised cause of morbidity in immunocompromised individuals. CMV seropositivity has been associated with signs of immunosenescence and systemic inflammation in the elderly. We aimed to assess the presence of CMV DNA in the blood of elderly and non-elderly patients with bronchial asthma. METHODS: Eighty five elderly asthmatics (above 65 years of age) and 74 younger asthma patients (aged 30-50) were recruited and underwent clinical and laboratory evaluation. Control group consisted of 63 adults over 65 years old and 56 subjects aged 30-50 without chronic respiratory disease. Real-time PCR (RT-PCR) for quantitation of CMV DNA was performed with the commercial CMV detection kit (detection limit > 500 copies/ mL) and with an in-house assay targeting the UL55gene (detection limit >100 copies/mL). RESULTS: Commercial CMV assay was positive in 18% of elderly and 1,3% non-elderly asthma patients, but was negative in all control samples. Custom made RT-PCR assay detected low levels of CMV DNA in 42.1% of asthma patients and in 12.6%, of control subjects (p<.001). The test positivity was higher in elderly asthmatics than in younger patients (52.9% vs. 29.7%, p5.003), and higher in elderly control subjects than in younger controls (22.2% vs. 1.8%, p<.001). Presence of CMV DNA was associated with an increased risk of asthma: OR55.1 [(95% CI: 2.7-9.4, p<.001)] for the whole population tested and OR521.6 [(95%CI: 2.8-166.1); p<.001)] for non-elderly subjects. CONCLUSIONS: CMV replication at low level is highly prevalent in elderly asthmatics and is associated with risk of asthma.