Total Inflammatory Cell Count Research Articles

Amelioration of bleomycin-induced pulmonary fibrosis in a mouse model by a combination therapy of bosentan and imatinib

ABSTRACTIntroduction: Idiopathic pulmonary fibrosis (IPF) is characterized by alveolitis, progressing into fibrosis. Due to the involvement of both endothelin and platelet-derived growth factor signaling in IPF, combination effects of a bosentan and imatinib were studied in mouse model of bleomycin-induced pulmonary fibrosis. Methods: Mice subjected to bleomycin instillation (0.05 U) and were administered with either bosentan (100 mg/kg) and/or imatinib (50 mg/kg). Inflammatory cell count, total protein estimation in bronchoalveolar lavage fluid, lung edema, superoxide dismutase, catalase, myeloperoxidase activities, and Hematoxylin & Eosin staining were performed on day 7. Hydroxyproline content, α-smooth muscle actin (SMA), collagens I and III gene expression analysis, immunohistochemistry, matrix metalloproteinases-9 and -2 activities, trichrome and sirius red staining were performed on day 21. Results: Combination treatment with bosentan and imatinib prevented bleomycin-induced mortality and loss of body weight more than the individual agents. On day 7, the combination therapy attenuated bleomycin-induced increase of total and differential inflammatory cell counts, total proteins, lung wet/dry weight ratio, myeloperoxidase activity, lung inflammatory cell infiltration more than individual agents alone. Bosentan but not imatinib ameliorated superoxide dismutase and catalase activities, which were lowered following bleomycin instillation. On day 21, combination therapy ameliorated bleomycin-induced increase of fibrosis score, collagen deposition, protein and gene expression of SMA, mRNA levels of collagens-I and -III, matrix metalloproteinase-9 and -2 activities more than monotherapy. Conclusion: Combination of bosentan and imatinib exerted more enhanced protection against bleomycin-induced inflammation and fibrosis than either of the agents alone.

Adjustment of sensitisation and challenge protocols restores functional and inflammatory responses to ovalbumin in guinea-pigs.

IntroductionInhalation of antigen in atopic asthma induces early (EAR) and late asthmatic responses (LARs), inflammatory cell infiltration and airways hyperresponsiveness (AHR). Previously, we have established a protocol of sensitisation and subsequent ovalbumin (Ova) inhalation challenge in guinea-pigs which induced these 4 features (Smith & Broadley, 2007). However, the responses of guinea-pigs to Ova challenge have recently declined, producing no LAR or AHR and diminished EAR and cells. By making cumulative modifications to the protocol, we sought to restore these features.MethodsGuinea-pigs were sensitised with Ova (i.p. 100 or 150 μg) on days 1 and 5 or days 1, 4 and 7 and challenged with nebulised Ova (100 or 300 μg/ml, 1 h) on day 15. Airway function was measured in conscious guinea-pigs by whole-body plethysmography to record specific airway conductance (sGaw). Airway responsiveness to aerosolized histamine (0.3 mM) was determined before and 24 h after Ova challenge. Bronchoalveolar lavage was performed for total and differential inflammatory cell counts. Lung sections were stained for counting of eosinophils.ResultsLack of AHR and LAR with the original protocol was confirmed. Increasing the Ova challenge concentration from 100 to 300 μg/ml restored AHR and eosinophils and increased the peak of the EAR. Increasing the number of sensitisation injections from 2 to 3 did not alter the responses. Increasing the Ova sensitisation concentration from 100 to 150 μg significantly increased total cells, particularly eosinophils. A LAR was revealed and lymphocytes and eosinophils increased when either the Al(OH)3 concentration was increased or the duration between the final sensitisation injection and Ova challenge was extended from 15 to 21 days.DiscussionThis study has shown that declining allergic responses to Ova in guinea-pigs could be restored by increasing the sensitisation and challenge conditions. It has also demonstrated an important dissociation between EAR, LAR, AHR and inflammation.

마황 추출물 투여가 Ovalbumin으로 유발된 마우스 알레르기성 천식에 미치는 영향

Objective : Ephedra sinica (ES) has has been used as remedy of allergic diseases for a long time in Korea. In the present study, we investigated the anti-allergic effects of ES on experimental allergic asthma mouse model using ovalbumin (OVA). Methods : BALB/c mice were sensitized and challenged with 100 ug of OVA and 1 mg of aluminum potassium sulfate of 0.2 ml phosphate-buffered saline(PBS) intraperitoneally on day 1 and 15. mice were challenged on 3 consecutive days with 5% OVA and AHR was assessed 24 h after the last challenge. we examined the lung histology, airway hyper sensitivity, total inflammatory cell count in bronchoaveloar lavage fluid(BALF), Th2-associated cytokines production and IgE production. Results : ES potently inhibited the lung damage and the development of Penh. ES also reduced the number of BAL cells during OVA-induced allergic asthma. Furthermore, ES inhibited cytokines production such as IL-4, IL-13 productions, and IgE level of serum. Conclusion : These results suggest that ES may inhibit the production of IL-4, IL-13, IgE and infiltration of inflammatory cell and be beneficial oriental medicine for allergic asthma.

Mangiferin attenuates TH1/TH2 cytokine imbalance in an ovalbumin-induced asthmatic mouse model.

Mangiferin is a major bioactive ingredient in Mangifera indica Linn. (Anacardiaceae) leaves. Aqueous extract of such leaves have been used as an indigenous remedy for respiratory diseases like asthma and coughing in traditional Chinese medicine. However, underlying molecular mechanisms of mangiferin on anti-asthma remain unclear. In our present study, we investigated the anti-asthmatic effect of mangiferin on Th1/Th2 cytokine profiles and explored its underlying immunoregulatory mechanism in mouse model of allergic asthma. Mangiferin significantly reduced the total inflammatory cell counts and eosinophil infiltration, decreased the production of ovalbumin-specific IgE in serum and PGD2 in BALF. The antibody array analysis showed that mangiferin down-regulated the levels of one group of cytokines/chemokines including Th2-related IL-4, IL-5, IL-13, and others IL-3, IL-9, IL-17, RANTES, TNF-α, but simultaneously up-regulated Th1-related IFN-γ, IL-2 and IL-10 and IL-12 expression in serum. Thus it attenuates the imbalance of Th1/Th2 cells ratio by diminishing the abnormal mRNA levels of Th1 cytokines (IFN-γ and IL-12) and Th2 cytokines (IL-4, IL-5 and IL-13). Finally, mangiferin substantially inhibited the activation and expression of STAT-6 and GATA-3 in excised lung tissues. Our results suggest that mangiferin can exert anti-asthmatic effect. The underlying mechanism may attribute to the modulation of Th1/Th2 cytokine imbalance via inhibiting the STAT6 signaling pathway.

Sputum ADAM8 expression is increased in severe asthma and COPD

Severe asthma and chronic obstructive pulmonary disease (COPD) are chronic inflammatory airway diseases in which the mechanisms are not fully understood. A disintegrin and metalloproteinase domain 8 (ADAM8) is an enzyme expressed on most leucocytes and may be important for facilitating leucocyte migration in respiratory disease. To investigate ADAM8 mRNA and protein expression in asthma and COPD and its relationship between asthma severity and inflammatory phenotypes. Induced sputum was collected from 113 subjects with asthma (severe n=31, uncontrolled n=39 and controlled n=35), 20 subjects with COPD and 21 healthy controls. Sputum ADAM8 mRNA expression was measured by qPCR, and soluble ADAM8 (sADAM8) protein was measured in the sputum supernatant by validated ELISA. ADAM8 mRNA correlated with ADAM8 protein levels (r=0.27, P<0.01). ADAM8 mRNA (P=0.004) and sADAM8 protein (P=0.014) levels were significantly higher in both asthma and COPD compared with healthy controls. ADAM8 mRNA (P=0.035) and sADAM8 protein (P=0.002) levels were significantly higher in severe asthma compared with controlled asthma. Total inflammatory cell count (P<0.01) and neutrophils (P<0.01) were also elevated in severe asthmatic sputum. Although ADAM8 mRNA was significantly higher in eosinophilic and neutrophilic asthma (P<0.001), sADAM8 did not differ between asthma inflammatory phenotypes. ADAM8 expression positively correlated with sputum total cell count and sputum neutrophils. ADAM8 expression is increased in both severe asthma and COPD and associated with sputum total cell count and neutrophils. ADAM8 may facilitate neutrophil migration to the airways in severe asthma and COPD.

Effects of taraxasterol on ovalbumin-induced allergic asthma in mice

Ethnopharmacological relevanceTaraxasterol was isolated from the Chinese medicinal herb Taraxacum officinale which has been frequently used as a remedy for inflammatory diseases. In the present study, we determined the in vivo protective effect of taraxasterol on allergic asthma induced by ovalbumin (OVA) in mice. Materials and methodsMice were sensitized and challenged with OVA, and were orally treated daily with taraxasterol at 2.5, 5 and 10mg/kg from day 23 to 27 after sensitization. The number of inflammatory cells in bronchoalveolar lavage fluid (BALF) was determined. Th2 cytokine interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-13 (IL-13) production in BALF and OVA-specific immunoglobulin E (IgE) production in sera were measured using ELISA. Histological changes in lung tissues were examined using hematoxylin and eosin (H&E) and periodic acid-Schiff staining (PAS). Airway hyperresponsiveness (AHR) to inhaled methacholine was assessed. ResultsTaraxasterol dramatically decreased the total inflammatory cell and main inflammatory cell counts, reduced the production of Th2 cytokine IL-4, IL-5, IL-13 in BALF and OVA-specific IgE in sera, and suppressed AHR in a dose-dependent manner. Histological studies demonstrated that taraxasterol substantially suppressed OVA-induced inflammatory cells infiltration into lung tissues and goblet cell hyperplasia in airways. ConclusionsThis finding suggests that taraxasterol protects against OVA-induced allergic asthma in mice.

Genetic replacement of surfactant protein-C reduces respiratory syncytial virus induced lung injury

BackgroundIndividuals with deficiencies of pulmonary surfactant protein C (SP-C) develop interstitial lung disease (ILD) that is exacerbated by viral infections including respiratory syncytial virus (RSV). SP-C gene targeted mice (Sftpc -/-) lack SP-C, develop an ILD-like disease and are susceptible to infection with RSV.MethodsIn order to determine requirements for correction of RSV induced injury we have generated compound transgenic mice where SP-C expression can be induced on the Sftpc -/- background (SP-C/Sftpc -/-) by the administration of doxycycline (dox). The pattern of induced SP-C expression was determined by immunohistochemistry and processing by Western blot analysis. Tissue and cellular inflammation was measured following RSV infection and the RSV-induced cytokine response of isolated Sftpc +/+ and -/- type II cells determined.ResultsAfter 5 days of dox administration transgene SP-C mRNA expression was detected by RT-PCR in the lungs of two independent lines of bitransgenic SP-C/Sftpc -/- mice (lines 55.3 and 54.2). ProSP-C was expressed in the lung, and mature SP-C was detected by Western blot analysis of the lavage fluid from both lines of SP-C/Sftpc -/- mice. Induced SP-C expression was localized to alveolar type II cells by immunostaining with an antibody to proSP-C. Line 55.3 SP-C/Sftpc -/- mice were maintained on or off dox for 7 days and infected with 2.6x107 RSV pfu. On day 3 post RSV infection total inflammatory cell counts were reduced in the lavage of dox treated 55.3 SP-C/Sftpc -/- mice (p = 0.004). The percentage of neutrophils was reduced (p = 0.05). The viral titers of lung homogenates from dox treated 55.3 SP-C/Sftpc -/- mice were decreased relative to 55.3 SP-C/Sftpc -/- mice without dox (p = 0.01). The cytokine response of Sftpc -/- type II cells to RSV was increased over that of Sftpc +/+ cells.ConclusionsTransgenic restoration of SP-C reduced inflammation and improved viral clearance in the lungs of SP-C deficient mice. The loss of SP-C in alveolar type II cells compromises their response to infection. These findings show that the restoration of SP-C in Sftpc -/- mice in response to RSV infection is a useful model to determine parameters for therapeutic intervention.

Spleen tyrosine kinase inhibition attenuates airway hyperresponsiveness and pollution-induced enhanced airway response in a chronic mouse model of asthma

Asthma is a chronic inflammatory disease characterized by airways hyperresponsiveness (AHR), reversible airflow obstruction, airway remodeling, and episodic exacerbations caused by air pollutants, such as particulate matter (PM; PM <2.5 μm in diameter [PM(2.5)]) and ozone (O(3)). Spleen tyrosine kinase (Syk), an immunoregulatory kinase, has been implicated in the pathogenesis of asthma. We sought to evaluate the effect of Syk inhibition on AHR in a chronic mouse model of allergic airways inflammation and pollutant exposure. We used a 12-week chronic ovalbumin (OVA) sensitization and challenge mouse model of airways inflammation followed by exposure to PM(2.5) plus O(3). Respiratory mechanics and methacholine (MCh) responsiveness were assessed by using the flexiVent system. The Syk inhibitor NVP-QAB-205 was nebulized intratracheally by using a treatment-based protocol 15 minutes before assessment of MCh responsiveness. Syk expression increased significantly in the airway epithelia of OVA-sensitized and OVA-challenged (OVA/OVA) mice compared with OVA-sensitized but PBS-challenged (OVA/PBS) control mice. OVA/OVA mice exhibited AHR to MCh, which was attenuated by a single administration of NVP-QAB-205 (0.3 and 3 mg/kg). PM(2.5) plus O(3) significantly augmented AHR to MCh in the OVA/OVA mice, which was abrogated by NVP-QAB-205. Total inflammatory cell counts were significantly higher in the bronchoalveolar lavage fluid from OVA/OVA than OVA/PBS mice and were unaffected by PM(2.5) plus O(3) or NVP-QAB-205. NVP-QAB-205 reduced AHR and the enhanced response to PM(2.5) plus O(3) to normal levels in an established model of chronic allergic airways inflammation, suggesting that Syk inhibitors have promise as a therapy for asthma.

Chrysin attenuates allergic airway inflammation by modulating the transcription factors T-bet and GATA-3 in mice

Chrysin, a flavonoid obtained from various natural sources, has been reported to possess anti-inflammatory, antitumor, antioxidant and anti-allergic activities. However, its anti-inflammatory and immunoregulatory activities in asthma animal models are poorly understood. In the present study, we examined the effects of chrysin on airway inflammation and the possible mechanisms through which it acts in a murine model of allergic asthma. BALB/c mice sensitized and challenged to ovalbumin (OVA) were administered intragastrically with chrysin at a dose of 50 mg/kg daily. Chrysin significantly suppressed OVA-induced airway hyperresponsiveness (AHR) to acetylcholine chloride (Ach). Chrysin administration significantly inhibited the total inflammatory cell and eosinophil counts in bronchoalveolar lavage fluid (BALF) and total immunoglobulin E (IgE) levels in serum. Histological examination of lung tissue demonstrated that chrysin significantly attenuated allergen-induced lung eosinophilic inflammation and mucus-producing goblet cells in the airway. In addition, chrysin triggered a switch of the immune response to allergens towards a T-helper type 1 (Th1) profile by modulating the transcription factors T-bet and GATA-3 in allergic mice. These data suggest that chrysin exhibits anti-inflammatory and immunoregulatory properties and provides new insights into the immunopharmacological role of chrysin in terms of its effects in a murine model of asthma.

C‐Abl Inhibition Exacerbates Mechanical Ventilation‐Induced Lung Injury In A Murine Model

Endothelial cytoskeleton is a contractile structure responsible for cellular responses to external stimuli and mechanical stress. Nonmuscle myosin light chain kinase (nmMLCK), a critical actin‐binding protein is required for trafficking of inflammatory cellsand alterations in permeability. c‐Abl kinase plays an essential role in barrier regulation via posttranslational modification of nmMLCK. Abl tyrosine kinase phosphorylates nmMLCK and regulates endothelial barrier function. We hypothesized that tyrosine kinase inhibitor imatinib, an anticancer agent, can exacerbate lung injury induced by mechanical ventilation (MV). To explore the role of c‐Abl in lung injury in vivo, mice were tested in our ventilation‐induced acute lung injury (VILI) model after imatinib. Mice were harvested 4h after MV. Imatinib significantly increased bronchoalveolar lavage protein levels (825ug/ml) and total inflammatory cell counts (1.07 × 10□) compared to sham (571ug/ml, 0.75 × 10μ) (p&lt;0.05). These preliminary results indicate that imatinib exacerbates VILI‐injury, likely via c‐Abl blockade. These studies have clinical relevance given the extensive use of imatinib as an anticancer agent and support an important functional role for c‐Abl in lung permeabilityFunded by: NIH grant: P01 HL58064

The effect of surgical denervation on prevention of excessive dermal scarring: A study on rabbit ear hypertrophic scar model

Previous reports have suggested that the extent of wound contraction, epithelisation and total healing time were influenced by denervation of tissues. In this article, we studied for the first time the effect of sensory denervation on prevention of excessive dermal scarring. Sixteen New Zealand white rabbits were used. Denervation of the right ears was performed by surgical excision of two main sensory nerves. Dissections were also performed on left ears without any nerve excision for the control group. After 14 days of follow-up and confirmation of tissue denervation, an excessive dermal scarring model as defined by Morris etal. was made by surgery on both ears. Twenty-eight days after making the wounds, the tissues were extirpated for analyses. The scars were evaluated by the scar elevation index (SEI), epithelisation time and inflammatory cell count. The SEI of the denervated side scars was significantly lower than that of the non-denervated side. The rate and timing of total epithelisation and inflammatory cell count between groups yielded no difference. In this study, the surgical denervation skin reduced scarring. It was suggested that understanding the exact role of sensory nerves and neural mediators in excessive dermal scarring is necessary for the prevention and treatment of scarring.

Level of Eosinophil Cationic Protein in Sputum of Chemical Warfare Victims

Objective(s) Considering fair response to inhaled corticosteroids and reports of severe air way hyper responsiveness in chemical warfare victims (CWV), a role for eosinophilic inflammation (i.e. asthma) was postulated. The objective of this study was to determine the presence of eosinophilic inflammation in CWV by evaluation of Sputum cellularity and eosinophil cationic protein (ECP). Materials and Methods Forty CWV and 15 control subjects entered this cross sectional study. Demographic data, dyspnea severity scale, spirometry results and 6 min walk test were determined. Sputum was collected with inducing by nebulizing hypertonic saline and analyzed for total inflammatory cell count, the cellular differential count and ECP level. Control group was normal volunteers with PC20 more than 8 mg/ml. Results Mean±SD of eosinophil percentage (11.7±11.1%) and ECP level in sputum of CWV (46.1±19.5 ng/ml) were significantly more than control group. Regression analysis showed significant correlation between ECP level and percentage of eosinophils in sputum (r= +0.43, P< 0.01). ECP level of CWV subjects with obstructive pattern did not show any significant difference from CWV with normal spirometry. ECP level in CWV subjects who revealed more than 12% improvement in forced expiratory volume in one second (FEV1) was significantly higher than CWV who had improvement less than 12% (P= 0.01). BO and asthma as final clinical diagnosis of CWV did not show any significant difference of sputum ECP. Conclusion Bronchial inflammation in different types of pulmonary complication of CWV is eosinophil dependent. ECP level of sputum in CWV could guide physician to select CWV who would respond to corticosteroids.

Grape Seed Proanthocyanidin Extract Attenuates Airway Inflammation and Hyperresponsiveness in a Murine Model of Asthma by Downregulating Inducible Nitric Oxide Synthase

Allergic asthma is characterized by hyperresponsiveness and inflammation of the airway with increased expression of inducible nitric oxide synthase (iNOS) and overproduction of nitric oxide (NO). Grape seed proanthocyanidin extract (GSPE) has been proved to have antioxidant, antitumor, anti-inflammatory, and other pharmacological effects. The purpose of this study was to examine the role of GSPE on airway inflammation and hyperresponsiveness in a mouse model of allergic asthma. BALB/c mice, sensitized and challenged with ovalbumin (OVA), were intraperitoneally injected with GSPE. Administration of GSPE remarkably suppressed airway resistance and reduced the total inflammatory cell and eosinophil counts in BALF. Treatment with GSPE significantly enhanced the interferon (IFN)- γ level and decreased interleukin (IL)-4 and IL-13 levels in BALF and total IgE levels in serum. GSPE also attenuated allergen-induced lung eosinophilic inflammation and mucus-producing goblet cells in the airway. The elevated iNOS expression observed in the OVA mice was significantly inhibited by GSPE. In conclusion, GSPE decreases the progression of airway inflammation and hyperresponsiveness by downregulating the iNOS expression, promising to have a potential in the treatment of allergic asthma.

Histopathologic characteristics of inferior turbinate vs ethmoidal polypin chronic rhinosinusitis

It seems apparently that the 2 separate anatomical areas (nasal cavity and paranasal sinus mucosa) are indeed one single unit with an identical behavior during inflammatory process. Similar histopathologic evidence in long-term condition could emphasize on the concept of rhinosinusitis in patients with inflammatory paranasal sinus disease. Prospective study was performed on 50 consecutive patients with polyposis in 2 different groups, one with and the other without asthma. Inferior turbine and polyp with ethmoid sinus origin were selected to compare the histopathologic findings of the surgical specimens from the 2 sites (affected sinus vs apparently unaffected nose). The general degree of inflammation, epithelial thickening, and inflammatory cell count were measured. The degree of inferior turbinate inflammation correlated with that of the ipsilateral polyp of ethmoid sinus in both groups. In addition, the total inflammatory cell count was comparable. There was no statistically significant difference in total polymorphonuclear, lymphocyte, and eosinophil count between the 2 sites in each group (P > .05). The ethmoid sinus inflammation in polypoid chronic sinusitis is accompanied by a proportionate inferior turbinate inflammation, not only in the patients with asthma but also in those with isolated sinonasal polyposis.

Protective Effect of Ambroxol against Paraquat-induced Pulmonary Fibrosis in Rats

To evaluate the possible therapeutic effect of ambroxol on pulmonary fibrosis induced by paraquat. Adult male Sprague-Dawley rats (n=144, 200-250 g) were divided into four groups (Control, Ambroxol, Paraquat, and Paraquat+Ambroxol group) and sacrificed on day 1, 3, 5, 7, 14 and 28. Several significant oxidant stress markers (MDA, SOD and GSH-PX), MPO activity, cytokines (TNF-α, MCP-1, TGF-β1, MMP-2 and TIMP-1), total inflammatory cell count, hydroxyproline content, collagen I and III mRNA were analyzed. In Paraquat group, the MDA, MPO activity, hydroxyproline contents, the mRNA expression of TNF-α, MCP-1, TGF-β1, MMP-2, TIMP-1, collagen I, collagen III and the number of total inflammatory cells were up-regulated in lung tissue, but SOD and GSH-PX activity were down-regulated in lung tissue compared with Control group (p<0.05). In paraquat+ambroxol group, the MDA, MPO activity, hydroxyproline content, the mRNA expression of TNF-α, MCP-1, TGF-β1, MMP-2, TIMP-1 collagen I, collagen III and the number of total inflammatory cells were significantly decreased, while the SOD and GSH-PX activities in lung tissue were increased compared with Paraquat group (p<0.05). Histological examination of paraquat-treated rats showed lung injury with interstitial edema and widespread inflammatory cell infiltration in the alveolar space and septum, as well as pulmonary fibrosis. Ambroxol could markedly reduce such damage in lung tissue and prevent pulmonary fibrosis. The results of this study indicated that ambroxol could reduce lung damage and prevent pulmonary fibrosis induced by paraquat.

Paeonol attenuates airway inflammation and hyperresponsiveness in a murine model of ovalbumin-induced asthma

Paeonol, the main active component isolated from Moutan Cortex, possesses extensive pharmacological activities such as anti-inflammatory, anti-allergic, and immunoregulatory effects. In the present study, we examined the effects of paeonol on airway inflammation and hyperresponsiveness in a mouse model of allergic asthma. BALB/c mice sensitized and challenged with ovalbumin were administered paeonol intragastrically at a dose of 100mg/kg daily. Paeonol significantly suppressed ovalbumin-induced airway hyperresponsiveness to acetylcholine chloride. Paeonol administration significantly inhibited the total inflammatory cell and eosinophil count in bronchoalveolar lavage fluid. Treatment with paeonol significantly enhanced IFN-γ levels and decreased interleukin-4 and interleukin-13 levels in bronchoalveolar lavage fluid and total immunoglobulin E levels in serum. Histological examination of lung tissue demonstrated that paeonol significantly attenuated allergen-induced lung eosinophilic inflammation and mucus-producing goblet cells in the airway. These data suggest that paeonol exhibits anti-inflammatory activity in allergic mice and may possess new therapeutic potential for the treatment of allergic bronchial asthma.

Interleukin 17 and RANTES levels in induced sputum of patients with allergic rhinitis after a single nasal allergen challenge

Interleukin 17 (IL-17) is produced by T(H)17 cells and was recently implicated in the development of the T(H)2 cell response. RANTES (regulated on activation of normal T cells expressed and secreted), among other chemokines, plays a crucial role in chemotaxis of eosinophils into airway mucosa. According to the "united airway" hypothesis, markers of inflammation in allergic diseases are elevated in the upper and lower airways. To assess the impact of a single nasal allergen challenge on IL-17 and RANTES levels in induced sputum of patients with allergic rhinitis (AR). Eighteen patients with a history of AR due to grass pollen confirmed by positive skin prick test results and 10 control subjects entered the study. Initially, all the patients underwent sputum induction. A single nasal placebo challenge was performed 24 hours later, with repeated sputum induction 24 hours after challenge. After 4 weeks of washout, these procedures were repeated with allergen challenge. Differential cell counts in sputum were determined, and concentrations of IL-17 and RANTES were measured by means of enzyme-linked immunosorbent assay. Levels of IL-17 and RANTES significantly increased in sputum of patients with AR after allergen (but not placebo) challenge (P = .03 and P = .007, respectively). Postallergen levels of both cytokines in sputum were positively correlated (r = 0.570, P = .02). Allergen challenge led to increased total inflammatory cell (P = .005) and eosinophil (P = .03) counts in induced sputum of patients with AR. Nasal allergen challenge induces the enhanced secretion of IL-17 and RANTES in the lower airways of nonasthmatic patients with AR.

Anti-fibrotic effect of thalidomide through inhibiting TGF-β-induced ERK1/2 pathways in bleomycin-induced lung fibrosis in mice

This study is designed to confirm the anti-fibrotic effect of thalidomide on bleomycin-induced lung fibrosis in a mouse model and to identify whether this anti-fibrotic effect is associated with inhibition of the transforming growth factor-beta (TGF-beta)-induced extracellular signal-regulated kinase1/2 (ERK1/2). C57BL/6 female mice were administered blomycin sulfate. In cultured human lung fibroblasts, expressions of type I collagen, fibronectin, and either TGF-beta or IL-6 were measured after thalidomide treatment by reverse transcription-polymerase chain reaction (RT-PCR). Expressions of ERK1/2, type I collagen, fibronectin, and TGF-beta1 from lung tissues of blomycin-induced mice and from mouse lung fibroblasts were evaluated using RT-PCR and western blotting. Thalidomide administration significantly inhibits TGF-beta1 mRNA expression in a dose-dependant manner following administration of IL-6 and IL-6R. In the analysis of BAL fluids, total BAL inflammatory cell counts, TGF-beta1, and IL-6 levels in thalidomide-treated mice were significantly reduced when compared with bleomycin-treated mice (p < 0.01, p < 0.01, and p < 0.001, respectively). Thalidomide inhibited total ERK1/2 and phospho-ERK1/2 expression after TGF-beta1 stimulation in the RT-PCR and western blotting. The results of our study suggest that the anti-fibrotic effect of thalidomide on lung fibrosis may be related to suppression of the TGF-beta1-induced ERK1/2 signaling pathway.

Eosinophilia-associated muscle disorders: an immunohistological study with tissue localisation of major basic protein in distinct clinicopathological forms

Aims:(a) To evaluate tissue eosinophil density, location of eosinophil cytotoxic products, histopathological muscle changes and inflammatory cell types in different eosinophilia-associated myopathies that are clinicopathologically heterogeneous. (b) To determine the...

Anti-inflammatory effects and clinical efficacy of theophylline and tulobuterol in mild-to-moderate chronic obstructive pulmonary disease

Background The airway inflammation of chronic obstructive pulmonary disease (COPD) demonstrates a poor response to the anti-inflammatory actions of corticosteroids. However, long-acting β 2-agonists and low-dose theophylline are reported to have a possible anti-inflammatory effect in COPD. The aim of this study was to compare the effects of treatment between theophylline and the tulobuterol patch (transdermal patch preparation designed to yield sustained β 2-agonistic effects for 24 h) on airway inflammation in addition to quality of life (QOL) and pulmonary function in mild-to-moderate COPD. Methods The study subjects consisted of 26 patients with COPD who were treated with theophylline or tulobuterol for 8 weeks with a wash-out period of 4 weeks in a randomized open-label crossover study. We prospectively investigated the differential cell counts and levels of inflammatory markers in induced sputum before and after treatment with theophylline and tulobuterol. We also examined pulmonary function and quality of life (QOL) as assessed by St. George's Respiratory Questionnaire. Results In the induced sputum, the total inflammatory cell count and number of neutrophils were significantly reduced by treatment with low-dose theophylline. Neither of these parameters was significantly changed by treatment with tulobuterol. Pulmonary function measurements such as FEV 1, FEV 1 %pred, FVC, PEF, MEF 50, and MEF 25 were significantly improved by the treatment with low-dose theophylline but not tulobuterol. The total QOL scores, levels of interleukin 8 and myeloperoxidase in the supernatants of induced sputum, and serum levels of hypersensitive C-reactive protein were not significantly changed by either of the treatments. Conclusion These results suggest that treatment with low-dose theophylline but not the tulobuterol patch may have anti-inflammatory effects and improve pulmonary function in mild-to-moderate COPD.