Mouse Model Of Acute Asthma Research Articles

LincR-PPP2R5C Promotes Th2 Cell Differentiation Through PPP2R5C/PP2A by Forming an RNA-DNA Triplex in Allergic Asthma.

The roles and mechanisms of long noncoding RNAs (lncRNAs) in T helper 2 (Th2) differentiation from allergic asthma are poorly understood. We aimed to explore a novel lncRNA, LincR-protein phosphatase 2 regulatory subunit B' gamma (PPP2R5C), in Th2 differentiation in a mouse model of asthma. LincR-PPP2R5C from RNA-seq data of CD4+ T cells of asthma-like mice were validated and confirmed by quantitative reverse transcription polymerase chain reaction, northern blotting, nuclear and cytoplasmic separation, and fluorescence in situ hybridization (FISH). Lentiviruses encoding LincR-PPP2R5C or shRNA were used to overexpress or silence LincR-PPP2R5C in CD4+ T cells. The interactions between LincR-PPP2R5C and PPP2R5C were explored with western blotting, chromatin isolation by RNA purification assay, and fluorescence resonance energy transfer. An ovalbumin-induced acute asthma model in knockout (KO) mice (LincR-PPP2R5C KO, CD4 conditional LincR-PPP2R5C KO) was established to explore the roles of LincR-PPP2R5C in Th2 differentiation. LncR-PPP2R5C was significantly higher in CD4+ T cells from asthmatic mice ex vivo and Th2 cells in vitro. The lentivirus encoding LincR-PPP2R5C suppressed Th1 differentiation; in contrast, the short hairpin RNA (shRNA) lentivirus decreased LincR-PPP2R5C and Th2 differentiation. Mechanistically, LincR-PPP2R5C deficiency suppressed the phosphatase activity of the protein phosphatase 2A (PP2A) holocomplex, resulting in a decline in Th2 differentiation. The formation of an RNA-DNA triplex between LincR-PPP2R5C and the PPP2R5C promoter enhanced PPP2R5C expression and activated PP2A. LincR-PPP2R5C KO and CD4 conditional KO decreased Th2 differentiation, airway hyperresponsiveness and inflammatory responses. LincR-PPP2R5C regulated PPP2R5C expression and PP2A activity by forming an RNA-DNA triplex with the PPP2R5C promoter, leading to Th2 polarization in a mouse model of acute asthma. Our data presented the first definitive evidence of lncRNAs in the regulation of Th2 cells in asthma.

Critical Involvement of CD44 in T Helper Type 2 Cell-Mediated Eosinophilic Airway Inflammation in a Mouse Model of Acute Asthma.

Interactions between CD44 and hyaluronan (HA) are crucial for recruiting leukocytes to inflamed tissues. This review summarizes findings from our studies of the roles of CD44-HA interactions in leukocyte trafficking, with a particular focus on airway T helper type 2 (Th2) cells in mouse models of acute asthma. In a mite allergen-induced model of acute asthma, intraperitoneal injection of anti-CD44 monoclonal antibodies blocked lymphocytes and eosinophils from accumulating in the lung, and suppressed both the antigen-induced increase in Th2 cytokines in the bronchoalveolar lavage fluid (BALF) and airway hyperresponsiveness (AHR). CD44 deficiency was associated with decreased mite allergen-induced Th2 cell-mediated airway inflammation and AHR in sensitized mice. Asthmatic responses to antigen-sensitized splenic CD4+ T cells transferred from CD44-deficient mice were weaker than in wild-type mice. Administration of anti-CD44 monoclonal antibodies preferentially suppressed the airway accumulation of antigen-specific Th2 cells induced by antigen challenge, without affecting Th1 and Th17 cells. Increased HA-binding ability of CD44 and expression of Neu1 sialidase were observed on antigen-specific Th2 cells compared with antigen-specific Th1 and Th17 cells. Finally, in a mouse model of acute asthma, neuraminidase 1-deficient SM/J mice exhibited a lower Th2 cytokine concentration and a lower absolute Th2 cell number in the BALF, as well as an attenuated AHR. Our findings indicate that CD44 critically contributes to the antigen challenge-induced airway accumulation of antigen-specific Th2 cells, without affecting Th1 and Th17 cells, in mice. Furthermore, neuraminidase 1 activity is necessary for the interaction between HA and CD44, and Th2 cell-mediated airway inflammation.

Evaluation of Human MSCs Treatment Frequency on Airway Inflammation in a Mouse Model of Acute Asthma.

BackgroundStudies in experimental models of allergic asthma have shown that mesenchymal stem cells (MSCs) have therapeutic potential for T-helper 2 (TH2) cell-mediated inflammation. However, the mechanisms underlying these therapeutic effects are not fully understood and their safety has not been confirmed.MethodsUsing a mouse model of experimental allergic asthma, we investigated the efficacy of human adipose-derived mesenchymal stem cells (hADSCs) or human bone marrow-derived mesenchymal stem cells (hBMSCs) according to treatment frequency and timing.ResultsOvalbumin (OVA)-sensitized and -challenged mice exhibited airway hyperresponsiveness (AHR), airway inflammation, and significant increases in TH2 cytokine levels. Both double and single human mesenchymal stem cell (hMSC) treatments significantly decreased AHR and bronchoalveolar lavage fluid counts. In addition, single treatment with hMSCs showed significant attenuation of allergic airway inflammation. However, double treatment with hMSCs during OVA -sensitization and -challenge further increased inflammatory cell infiltration, and TH2 cytokine levels.ConclusionThe results of treatment with hADSCs or hBMSCs suppresses AHR and airway inflammation. However, double hMSC treatment significantly induces eosinophilic airway inflammation and lung histological changes. Therefore, double hMSC treatment is ineffective against asthma and single injection frequency appears to be more important for the treatment of asthma. These results suggest that hMSC therapy can be used for treatment of asthma patients but that it should be used carefully.

Saxagliptin mitigates airway inflammation in a mouse model of acute asthma via modulation of NF-kB and TLR4

Saxagliptin (Saxa), a dipeptidyl dipeptidase-4 (DPP-4) inhibitor, is widely used for the treatment of type 2 diabetes mellitus. It has been documented to have immunomodulatory and anti-inflammatory actions. Our objective was to delineate the protective effect and the underlying mechanism of Saxa-in comparison with Dexamethasone (Dexa) – in airway inflammation induced by ovalbumin (OVA) in mice. MethodsMice were OVA-sensitized and challenged for the induction of acute asthma. Mice were orally administrated Saxa or Dexa. Total and differential cell counts, lactate dehydrogenase (LDH) and total protein concentrations were assessed in bronchoalveolar lavage fluid (BALF). The toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-kB), reduced glutathione (GSH), and total nitrate/nitrite products (NOx) levels as well as myeloperoxidase (MPO) activity in lung tissues were measured. Histopathological examination of the lung specimens was carried out using the hematoxylin and eosin (H & E) staining. ResultsHistopathological examination revealed that both Saxa and Dexa ameliorated OVA-induced inflammatory changes and significantly reduced total and differential leukocyte counts, LDH and total protein level in BALF upon comparison with OVA group. In addition, both treatments significantly mitigated OVA-induced oxidative stress as evidenced by diminished lung NOx level and MPO activity and elevated GSH level. The elevation of TLR4 and NF-kB levels in lung tissue were ameliorated by Saxa and Dexa administration. ConclusionSaxa had marked antiasthmatic effect in OVA-induced allergic asthma through modulation of TLR4 and NF-κB signaling. Also, Saxa may represent a promising therapeutic agent for acute allergic asthma.

Next Generation Sequencing for Long Non-coding RNAs Profile for CD4+ T Cells in the Mouse Model of Acute Asthma.

Background and AimsAlthough long non-coding RNAs (lncRNAs) have been linked to many diseases including asthma, little is known about lncRNA transcriptomes of CD4+ T cells in asthma. The present study aimed to explore the lncRNAs profile in the CD4+T cells from the mouse model of acute asthma.MethodsNext generation sequencing for lncRNAs and mRNAs was performed on CD4+ T cells from asthma and control mice. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathway analyses were performed to predict the functions and signal pathways for the aberrant lncRNAs. The selected lncRNAs were further measured using quantitative real-time PCR (polymerase chain reaction) and observed in the fluorescence in situ hybridization (FISH). The lncRNA–mRNA co-expression network was constructed via Pearson’s correlation coefficient and Cytoscape 3.6.ResultsNext generation sequencing revealed 36 up-regulated lncRNAs and 98 down-regulated lncRNAs in acute asthma compared with controls. KEGG pathway analysis showed that cytokine-cytokine receptor interaction had the highest enrichment scores. A co-expression network was constructed in which 23 lncRNAs and 301 mRNAs altered formed a total of 12424 lncRNA and mRNA pairs. To validate the RNA sequencing results, we measured the 4 different lncRNAs using qPCR. The lncRNA fantom3_9230106C11 was significantly reduced in CD4+ T cells of asthma. Bioinformatics analysis showed that lncRNA fantom3_9230106C11 had the potential to interact with many miRNAs and transcription factors related to Th2 differentiation.ConclusionThis study provided the first evidence for different expression of lncRNAs of CD4+T cells in asthma and may serve as a template for further, larger functional in-depth analyses regarding asthma molecular lncRNAs.

Effect of nintedanib on airway inflammation in a mouse model of acute asthma

Objective: New treatments are needed for cases of asthma that are refractory to traditional therapies. In this study, we examined the effect of oral nintedanib, an intracellular inhibitor of tyrosine kinases, on airway hyper-responsiveness (AHR) and airway smooth muscle cells, using a mouse model of experimental asthma. Methods: Asthma was experimentally induced in mice via subcutaneous injection of ovalbumin (OVA). A group of saline-injected mice served as a control group. The OVA mice were then divided into four treatment groups according to the dose of nintedanib. AHR was examined via exposure to vaporized methacholine. Airway inflammation was assessed via bronchoalveolar lavage fluid (BALF) cell counts and Th2 cytokine concentrations. Results: Baseline levels of AHR and airway inflammation were higher in OVA mice than in the control group. Treatment with nintedanib lowered AHR, BALF cell counts and BALF cytokine levels in a dose-dependent fashion. The effect of nintedanib was comparable to that of dexamethasone. In particular, treatment with nintedanib lowered the expression of transforming growth factor-β1 and inhibited the expression and phosphorylation of platelet-derived growth factor receptor-β, vascular endothelial growth factor receptor 1 (VEGFR1), VEGFR2, fibroblast growth factor receptor 2 (FGFR2), FGFR3, and extracellular signal-regulated kinase. Conclusions: Nintedanib lowered AHR and the expression of factors associated with airway inflammation and remodeling in a mouse model of experimental asthma. Our results suggest that nintedanib may be useful in the treatment of asthma.

Baicalin attenuates inflammation in mice with OVA-induced asthma by inhibiting NF-κB and suppressing CCR7/CCL19/CCL21.

Baicalin, extracted and purified from the Chinese medicinal plant, ScutellariabaicalensisGeorgi(Huangqin in Chinese), exhibits potent anti-inflammatoryactivity against asthma. However, it remains unknown whether baicalin inhibits the activity of CCchemokinereceptor7(CCR7) and its ligands, which are crucial for the initiation of airway inflammation. In the present study, we investigated the effects of baicalin on CCR7 and its ligands, CCL19 andCCL21, as well as on the nuclear factor-κB(NF-κB)pathway in a mouse model of asthma. A mouse model of acute asthma was established by exposing the mice to ovalbumin(OVA) (by intraperitoneal injection and inhalational challenge). Within 24h of the final OVAchallenge, lung function was detected by direct airway resistance analysis. Lung tissues were examined for pathological changes. Inflammatory cell counts in bronchoalveolar lavage fluid(BALF) were assessed. ELISA was utilized to evaluate the OVA-IgE, CCL19 and CCL21 levels in BALF. The interleukin(IL)-6and tumor necrosis factor(TNF)-α levels in serum were also detected by ELISA. The protein expression levels of CCR7, as well as that of phosphorylatedIκBα(p-IκBα) and phosphorylatedp65(p-p65) were determined by western blot analysis and RT-qPCR was used to determine the CCR7mRNA levels. Our data demonstrated that the oral administration of baicalin significantly improved pulmonaryfunction and attenuated inflammatory cell infiltration into the lungs. Baicalin also decreased the levels of OVA-IgE, IL-6, TNF-α and CCR7, as well as those of its ligand, CCL19; the levels of NF-κB were also markedly suppressed by baicalin. The CCR7mRNA level was substantially decreased. Our results thus suggest that baicalin exerts an inhibitory effect on airwayinflammation, and this effect may be associated with the inhibition of CCR7 and CCL19/CCL21, which may provide new mechanistic insight into the anti‑inflammatoryeffects of baicalin.

Comparative study of Korean White Ginseng and Korean Red Ginseng on efficacies of OVA-induced asthma model in mice

BackgroundKorean ginseng is a well-known medicinal herb that has been widely used in traditional medicine to treat various diseases, including asthma. Ginseng can be classified as white ginseng (WG) or red ginseng (RG), according to processing conditions. In this study, the authors compared the efficacies of these two ginseng types in a mouse model of acute asthma. MethodsTo produce the acute asthma model, BALB/c mice were sensitized with ovalbumin (OVA) and aluminum hydroxide, and then challenged with OVA. WG and RG extracts were administered to mice orally. The influences of WG and RG on airway hyperresponsiveness (AHR), immune cell distributions in bronchoalveolar lavage fluid (BALF), and OVA-specific immunoglobulin E (IgE), IgG1, and IgG2a in serum were investigated. Cytokine production by lymphocytes isolated from peribronchial lymph nodes and histopathological changes was also examined. ResultsIn OVA-sensitized mice, both WG and RG reduced AHR and suppressed immune cell infiltration in bronchoalveolar regions. BALF OVA-specific IgE levels were significantly lower in RG-treated OVA-sensitized mice than in the OVA-sensitized control group. WG and RG also suppressed inflammatory cytokine production by peribronchial lymphocytes. Histopathological findings showed reduced inflammatory cell infiltration and airway remodeling (e.g., epithelial hyperplasia) in WG- and RG-treated OVA mice compared with OVA controls. ConclusionIn this study, WG and RG showed antiasthmatic effects in an OVA-sensitized mouse model, and the efficacies of RG were found to be better than those of WG.

Population of sensory neurons essential for asthmatic hyperreactivity of inflamed airways.

Asthma is a common debilitating inflammatory lung disease affecting over 200 million people worldwide. Here, we investigated neurogenic components involved in asthmatic-like attacks using the ovalbumin-sensitized murine model of the disease, and identified a specific population of neurons that are required for airway hyperreactivity. We show that ablating or genetically silencing these neurons abolished the hyperreactive broncho-constrictions, even in the presence of a fully developed lung inflammatory immune response. These neurons are found in the vagal ganglia and are characterized by the expression of the transient receptor potential vanilloid 1 (TRPV1) ion channel. However, the TRPV1 channel itself is not required for the asthmatic-like hyperreactive airway response. We also demonstrate that optogenetic stimulation of this population of TRP-expressing cells with channelrhodopsin dramatically exacerbates airway hyperreactivity of inflamed airways. Notably, these cells express the sphingosine-1-phosphate receptor 3 (S1PR3), and stimulation with a S1PR3 agonist efficiently induced broncho-constrictions, even in the absence of ovalbumin sensitization and inflammation. Our results show that the airway hyperreactivity phenotype can be physiologically dissociated from the immune component, and provide a platform for devising therapeutic approaches to asthma that target these pathways separately.

IL-33 promotes mouse keratinocyte-derived chemokine, an IL-8 homologue, expression in airway smooth muscle cells in ovalbumin-sensitized mice.

Although it is recognized that IL-33 plays a key role in the onset of asthma, it is currently unclear whether IL-33 acts on any other target cells besides mast cells and Th2 cells in asthma. We investigated that whether airway smooth muscle cells (ASMCs) could contribute to asthma via stimulation with IL-33. To create a mouse model of acute asthma, murine ASMCs were isolated and cultured in vitro with IL-33. The ASMCs were divided into two groups, ASMCs from normal mice and ASMCs from ovalbumin-sensitized mice. The release of mouse KC was analyzed by PCR and ELISA. Immunocytochemical Staining of murine ASMCs for ST2 and IL-1RAcP was performed. IL-33 promoted KC expression, both in terms of mRNA and protien levels, in ASMCs from ovalbumin-sensitized mice. ST2 and IL-1RAcP were expressed in the membrane of ASMCs in ovalbumin-sensitized mice. IL-33 may contribute to the inflammation in the airways by acting on airway smooth muscle cells. IL-33 and ST2 may play important roles in allergic bronchial asthma.

The effect of HSP70/CD80 DNA vaccine on airway inflammation by regulating the chemokine and the receptor of chemokine in asthmatic mice

Objective To determine the effect of HSP70/CD80 DNA vaccine on airway inflammation and airway hyperresponsiveness in asthma mice through regulating Th1/Th2 balance in the chemokine and its receptor.Methods Mouse model of acute asthma was established by OVA-sensitized.At the same time,mice were injected with HSP70/CD80 DNA vaccine for observing airway responsiveness (AR),detecting serum IgE,measuring the pathological changes of lung tissue,and detecting CCL5 and CCL17 expression.The expression levels of CCR5 and CCR4 mRNA in lung tissue were examined using real-time PCR.Results Compared with the control mice,mice with acute asthma showed a significant increase in airway reactivity and the infiltration of inflammatory cells in lung tissue.Mice treated with HSP70/CD80 DNA vaccine could effectively reduce airway hyperresponsiveness in airway,as well as the perivascular inflammatory response (P＜0.05).The expression of CCL5 was positive in airway epithelia,while CCL17 was negative (P＜0.05).CCR5 gene expression in lung tissue was increased,while CCR4 expression was decreased (P＜0.05).Conclusion HSP70/CD80 DNA vaccine could treat asthma through restoring Th1/Th2 balance in two regulation ways,of which one was by enhancing the expression of CCL5 in airway epithelial cell and reducing CCL17 expression,the other was up-regulating the ratio of CCR5/CCR4 via increasing the expression of CCR5 and decreasing the expression of CCR4. Key words: Asthma; Airway inflammation; CCR4; CCR5; CCL5; CCL17

Interleukin-13 peptide kinoid vaccination attenuates allergic inflammation in a mouse model of asthma

Asthma is an atopic disorder with increasing frequency and severity in developed nations. Interleukin-13 (IL-13) is one of the most critical mediators of asthma pathology. In the present study, we developed a vaccine comprised of a keyhole limpet hemocyanin-mIL-13 heterocomplex immunogen to persistently neutralize excessive endogenous IL-13. Our results showed that the IL-13 peptide kinoid vaccine could induce sustained and high titer of IL-13-specific IgG when using aluminum hydroxide as an adjuvant, and could suppress the accumulation of eosinophils as well as IL-13 levels in bronchoalveolar lavage fluid (BALF). In addition, total IgE and ovalbumin (OVA)-specific IgE in serum were significantly inhibited. This study also showed that vaccination could prevent airway inflammation and epithelial cell proliferation with goblet cell hyperplasia in a mouse model of acute asthma. In summary, our findings suggest that the IL-13 peptide kinoid can serve as an innovative and effective vaccine against asthma.

The Role of Natural Killer T Cells in the Pathogenesis of Acute Exacerbation of Human Asthma

Background: Natural killer T (NKT) cells have been reported to play a crucial role in the pathogenesis of asthma in a mouse model of acute asthma. The present study aimed to investigate the role of NKT cells in the immune pathogenesis of acute exacerbation of human asthma. Methods: Blood and sputum were obtained at baseline and 8 h after a challenge in 20 asthmatics who underwent allergen bronchial provocation testing and during exacerbation and convalescence in 9 asthmatics who were admitted to hospital with an acute exacerbation after an upper respiratory tract infection. 6B11+ or Vα24+ NKT cells were measured with flow cytometry. Inflammatory cells, cytokines and chemokines were determined in sputum. Results: The number of blood NKT cells did not change after a positive allergen challenge compared to the baseline. However, blood CD4+Vα24+ NKT cells decreased during infection-associated asthma exacerbations compared to the convalescence measurements of the same patients (p < 0.05) or the baseline measurements of asthmatics who underwent allergen challenges (p < 0.01). The number of sputum NKT cells did not change after a positive allergen challenge or during infection-associated asthma exacerbations. Eosinophils and various cytokines and chemokines increased in sputum during infection-associated asthma exacerbations. Blood CD4+Vα24+ NKT cells were inversely related to sputum eosinophils (Spearman’s correlation coefficient = –0.62; p < 0.01). Conclusion: Blood NKT cells decreased during infection-associated asthma exacerbation and were inversely associated with eosinophilic airway inflammation, suggesting that blood NKT cells might be mobilized to the airways and lungs during asthma exacerbation in humans.

Mimotope vaccination for therapy of allergic asthma: anti‐inflammatory effects in a mouse model

One of the concerns of allergen-specific immunotherapy is the possible boost of inflammatory allergen-specific T lymphocytes. To address this problem, treatment with B cell epitopes devoid of allergen-specific T cell epitopes would be a promising alternative. In this study, we examined the therapeutic potency of a single mimotope, mimicking a structural IgE epitope of grass pollen allergen Phl p 5 in an established memory mouse model of acute allergic asthma. In the experimental set-up, BALB/c mice were primed with intraperitoneal injections of recombinant Phl p 5a (rPhl p 5a) and subsequently aerosol challenged with the nebulized allergen. Mice developed signs of bronchial asthma including hypereosinophilia around bronchi, goblet cell hyperplasia and enhanced mucus production. When the mice were subsequently treated with the grass pollen mimotope coupled to keyhole limpet haemocyanin, bronchial eosinophilic inflammation and mucus hypersecretion decreased. Further, a decrease of Th2 cytokines IL-4 and IL-5 could be observed in the bronchoalveolar lavage (BAL). In contrast to rPhl p 5a, the mimotope was in vitro not able to stimulate splenocytes to proliferation or IL-5 production. Despite not affecting the levels of pre-existing IgE, vaccination with the single mimotope thus rendered anti-inflammatory effects in a mouse model of acute asthma. From our data, we conclude that vaccination with a mimotope peptide representing a single IgE epitope of the allergen Phl p 5a and being devoid of allergen-specific T cell epitopes is able to down-regulate inflammation in acute asthma.

EDITORIAL

I am pleased to announce that Dr Jeremy Brown has recently joined our team of Associate Editors. Dr Brown is Senior Lecturer at the Centre for Respiratory Research at the University College London and his main area of research is the molecular pathogenesis of infections due to Streptococcus pneumoniae and the mechanisms of lung innate immunity. His main clinical interests are infectious diseases affecting the lung, including pneumonia, bronchiectasis, tuberculosis and infections in the immuno-compromised host. We are looking forward to his contribution to the Journal. The Editorial Office team needs to expand due to the significant growth in the Journal and employing some extra staff is long overdue. We are pleased to welcome Dr Christel Norman back from maternity leave. She will be working part-time in the Editorial Office, providing valuable assistance in managing the Journal. We are equally delighted to welcome Ms Joyanne Kelly to the Editorial Office team. Joyanne has just submitted her PhD at The University of Western Australia in the field of applied cancer research. She will take over the Administrative Editor role from Dr Neil Misso, who has relinquished this part of his Editorial Office duties. Neil's assistance over the past year has been invaluable and we are pleased that he will continue to contribute his expertise to the Journal through editing accepted papers. The first highlight in this issue is the paper ‘Evaluation of the anti-inflammatory effect of infliximab in a mouse model of acute asthma’ by Dr Deveci and colleagues, showing that the anti-tumour necrosis factor (TNF)-α mAb (infliximab) has a considerable anti-inflammatory effect on allergen-induced lung inflammation. This study emphasizes the potential for inhibition of TNF-α with infliximab as a therapeutic strategy. The second highlight in this issue, ‘Common functional polymorphisms in the cathepsin S promoter in Japanese subjects: Possible contribution to pulmonary emphysema’ by Dr Minematsu and colleagues, identifies novel functional polymorphisms in the cathepsin S gene, which has a possible association with pulmonary emphysema in the Japanese population. In ‘Procalcitonin is a valuable prognostic marker in ARDS caused by community-acquired pneumonia’, Dr Tseng and colleagues evaluate the role of procalcitonin in predicting the outcome of patients with ARDS caused by severe community-acquired pneumonia and confirmed it is a valuable biomarker for predicting mortality. The following two highlights in this issue present the results of literature meta-analyses. The meta-analysis performed by Dr Shi and colleagues in ‘Diagnostic value of carcinoembryonic antigen in malignant pleural effusion: A meta-analysis’ shows that carcinoembryonic antigen measurement is a useful tool in the diagnosis of malignant pleural effusions, and can assist in differentiating between malignant pleural mesothelioma and metastatic lung cancer. The second meta-analysis ‘Observational studies on the effect of dietary antioxidants on asthma: A meta-analysis’, undertaken by Professor Gao and colleagues, examines the association between dietary intake of the antioxidants vitamins C and E and β carotene, and the risk of asthma. The paper by Dr Hallani and colleagues ‘Enforced mouth breathing decreases lung function in mild asthmatics’ explores the impact of mouth versus nose breathing in a group of mild asthmatic subjects at rest. This study demonstrates that enforced oral breathing causes a decrease in lung function in these asthmatics, with some subjects initiating asthma symptoms. In ‘Arterial blood lactate is a useful guide to when rehabilitation should be instigated in COPD’, Dr Tanaka and colleagues evaluated the increase in lactate concentration during the early phase of exercise as an index for determining when to start pulmonary rehabilitation in COPD patients, as well as for determining muscle fatigue in the lower extremities of those patients undergoing rehabilitation. In the Short Communication ‘Neutrophil elastase activity in acute lung injury and respiratory distress syndrome’, Dr Hashimoto and colleagues investigate the role of neutrophil elastase in acute lung injury and acute respiratory distress syndrome, by treating patients with the selective neutrophil inhibitor sivelestat. Finally, the technical report by Dr Pinto and colleagues ‘Diagnosis of pulmonary aspiration—a mouse model using a starch granule test in bronchoalveolar lavage’ shows that the detection of starch granules in bronchoalveolar lavage may be a more specific way of diagnosing pulmonary aspiration in children than the less specific lipid-laden macrophages method, which is currently used in clinical practice. I hope you will enjoy this issue of Respirology.

Evaluation of the anti‐inflammatory effect of infliximab in a mouse model of acute asthma

To evaluate the potential role of anti-tumour necrosis factor (TNF)-alpha mAb (infliximab) on the inflammatory response in a mouse model of acute asthma. BALB/c mice received intraperitoneal (i.p.) ovalbumin (OVA) on days 0 and 14, 100 microg of OVA intranasally on day 14 and 50 microg of OVA intranasally on days 25, 26 and 27. The low-dose (2.5 mg/kg) and high-dose (6.25 mg/kg) infliximab groups received i.p. infliximab before each i.p. sensitization and on challenge days 1, 6, 13, 20 and 27. The control group received i.p. injections of normal saline with alum on days 0 and 14 and normal saline without alum on days 14, 25, 26 and 27. There were statistically significant decreases in the numbers of BAL fluid (BALF) neutrophils, eosinophils, as well as lung eosinophils in both the low- and high-dose infliximab groups when compared with the control OVA sensitized/challenged group. The lower dose of infliximab did not alter lung neutrophil counts, but a marked decrease was seen with the high dose of infliximab. After treatment with low and high doses of infliximab, BALF levels of regulated on activation normal T cell expressed and secreted (RANTES), granulocyte macrophage-colony stimulating factor (GM-CSF), TNF-alpha, IL-6, macrophage inflammatory protein (MIP)-2, and levels of RANTES, IL-4, GM-CSF, TNF-alpha, IL-6 and MIP-2 in lung tissue were significantly decreased when compared with the control OVA sensitized/challenged group. There was a significant decrease in BALF IL-4 only in the high-dose infliximab group. These results show that an anti-TNF-alpha mAb has a considerable anti-inflammatory effect on allergen-induced lung inflammation in an animal model of acute asthma.