(1/408) Immunomodulatory role of C10 chemokine in a murine model of allergic bronchopulmonary aspergillosis.
The immunomodulatory role of the chemokine C10 was explored in allergic airway responses during experimental allergic bronchopulmonary aspergillosis (ABPA). The intratracheal delivery of Asperigillus fumigatus Ag into A. fumigatus-sensitized mice resulted in significantly increased levels of C10 within the bronchoalveolar lavage, and these levels peaked at 48 h after A. fumigatus challenge. In addition, C10 levels in BAL samples were greater than 5-fold higher than levels of other chemokines such as monocyte-chemoattractant protein-1, eotaxin, and macrophage-inflammatory protein-1alpha. From in vitro studies, it was evident that major pulmonary sources of C10 may have included alveolar macrophages, lung fibroblasts, and vascular smooth muscle cells. Experimental ABPA was associated with severe peribronchial eosinophilia, bronchial hyperresponsiveness, and augmented IL-13 and IgE levels. The immunoneutralization of C10 with polyclonal anti-C10 antiserum 2 h before the intratracheal A. fumigatus challenge significantly reduced the airway inflammation and hyperresponsiveness in this model of ABPA, but had no effect on IL-10 nor IgE levels. Taken together, these data suggest that C10 has a unique role in the progression of experimental ABPA. (+info)
(2/408) Long term prevention of allergic lung inflammation in a mouse model of asthma by CpG oligodeoxynucleotides.
Asthma is an inflammatory disease of the airways that is induced by Th2 cytokines and inhibited by Th1 cytokines. Despite a steady increase in the incidence, morbidity, and mortality from asthma, no current treatment can reduce or prevent asthma for a prolonged period. We examined the ability of unmethylated CpG oligodeoxynucleotides (ODN), which are potent inducers of Th1 cytokines, to prevent the inflammatory and physiological manifestations of asthma in mice sensitized to ragweed allergen. Administration of CpG ODN 48 h before allergen challenge increased the ratio of IFN-gamma to IL-4 secreting cells, diminished allergen-induced eosinophil recruitment, and decreased the number of ragweed allergen-specific IgE-producing cells. These effects of CpG ODN were sustained for at least 6 wk after its administration. Furthermore, there was a vigorous Th1 memory response to the recall Ag, inhibition of peribronchial and perivascular lung inflammation, and inhibition of bronchial hyperresponsiveness 6 wk after administration of CpG ODN. Administration of CpG ODN in IFN-gamma -/- mice failed to inhibit eosinophil recruitment, indicating a critical role of IFN-gamma in mediating these effects. This is the first report of a treatment that inhibits allergic lung inflammation in presensitized animals for a prolonged period and thus has relevance to the development of an effective long term treatment for asthma. (+info)
(3/408) Pulmonary eosinophilia associated with montelukast.
Antileukotriene drugs are new therapeutic agents that have recently been approved for the treatment of asthma. Several cases of eosinophilic conditions including Churg-Strauss syndrome have been reported to be associated with zafirlukast, a cysteinyl leukotriene type 1 receptor antagonist. So far no other leukotriene modifier has been associated with the syndrome. The case history is presented of a man with allergic rhinitis and asthma who had received intermittent pulse therapy with oral corticosteroids. Pulmonary eosinophilia developed while he was receiving treatment with montelukast, a chemically distinct cysteinyl leukotriene type 1 receptor antagonist. After discontinuation of montelukast therapy and administration of systemic corticosteroids the patient's symptoms reversed rapidly and there was prompt resolution of the pulmonary infiltrates. We believe that cysteinyl leukotriene type 1 receptor antagonists are safe and effective drugs for most patients with asthma but caution is needed for those with more severe disease who require systemic corticosteroids, especially if they show characteristics of the atypical allergic diathesis seen in the prodromal phase of Churg-Strauss syndrome. (+info)
(4/408) Short ragweed allergen induces eosinophilic lung disease in HLA-DQ transgenic mice.
The human leukocyte antigen (HLA) restriction of the IgE response to different allergens in humans has been a subject of numerous published studies. However, the role and contribution of specific HLA class II molecules in the pathogenesis of allergic airway inflammation are unknown and difficult to assess. HLA-DQ6 and HLA-DQ8 transgenic mice lacking endogenous mouse class II gene expression were actively immunized and later challenged intranasally with short ragweed (SRW) allergenic extract. The HLA-DQ transgenic mice developed pulmonary eosinophilia and lung tissue damage. We also found an increase in total protein (TP) level and IL-5 production in bronchoalveolar lavage (BAL) fluid and an increase in SRW-specific Th2-type immunoglobulins (IgG1, IgG2b) and total serum IgE levels. Under similar treatment, DQ-negative full-sib control mice were normal. The allergic response could be significantly inhibited or abrogated in HLA-DQ mice by systemic treatment with anti-DQ mAb. The in vivo responses of HLA-DQ6 and HLA-DQ8 mice showed differences in terms of levels of eosinophilia, BAL protein, IL-5 concentration, and lung hyperreactivity to inhaled methacholine. These findings demonstrate the crucial role for specific HLA-DQ molecules in SRW-specific CD4(+) T-cell activation and resulting recruitment of eosinophils into the airways. (+info)
(5/408) Eosinophilic pneumonia with eosinophilic gastroenteritis.
A 48-year-old man was admitted to our hospital with cough, fever and dysphagia. He had a past history of bronchial asthma and surgery for nasal polyp. Chest radiograph and computed tomography showed atelectasis in the right lower field and infiltrative shadow in the left lower field and overall thickening of the esophageal wall. Transbronchial lung biopsy (TBLB) specimens revealed infiltration of eosinophils and lymphocytes under the bronchial mucosa. Gastrointestinal tract biopsy specimens showed submucosal infiltration of eosinophils. These findings led to a definite diagnosis of eosinophilic pneumonia associated with eosinophilic gastroenteritis, a disease which has been rarely reported. (+info)
(6/408) Montelukast reduces airway eosinophilic inflammation in asthma: a randomized, controlled trial.
Leukotrienes are pro-inflammatory mediators which may contribute to tissue, sputum, and blood eosinophilia seen in allergic and inflammatory diseases, including asthma. Montelukast is a cysteinyl leukotriene1 (CysLT1) receptor antagonist which improves asthma control; the aim of this study was to investigate its effect on induced sputum eosinophils. Montelukast 10 mg (n=19) or placebo (n=21) were administered orally once in the evening for 4 weeks to 40 chronic adult asthmatic patients, aged 19-64 yrs, in a double-blind, randomized, parallel group study. Patients were included if, at prestudy, they had >5% sputum eosinophils, symptomatic asthma with a forced expiratory volume in one second > or =65% of the predicted value and were being treated only with "as needed" inhaled beta2-agonists. In addition to sputum eosinophils, blood eosinophils and clinical endpoints were also assessed. Four weeks of montelukast treatment decreased sputum eosinophils from 7.5% to 3.9% (3.6% decrease, 95% confidence interval (CI) -16.6-0.4). In contrast, placebo treatment was associated with an increase in sputum eosinophils from 14.5% to 17.9% (3.4% increase, 95% CI -3.5-9.8). The least squares mean difference between groups (-11.3%, 95% CI -21.1-(-1.4)) was significant (p=0.026). Compared with placebo, montelukast significantly reduced blood eosinophils (p=0.009), asthma symptoms (p=0.001) and beta2-agonist use (p<0.001) while significantly increasing morning peak expiratory flow (p=0.001). Montelukast was generally well tolerated in this study, with a safety profile similar to the placebo. These results demonstrate that montelukast decreases airway eosinophilic inflammation in addition to improving clinical parameters. Its efficacy in the treatment of chronic asthma may be due, in part, to the effect on airway inflammation. (+info)
(7/408) Repetitive hyperpnoea causes peripheral airway obstruction and eosinophilia.
Hyperpnoea of canine peripheral airways with dry air results in airway obstruction, mucosal damage, and inflammation. The purpose of this study was to evaluate the effect of repeated dry air challenge (DAC) on airway obstruction, reactivity and the development of airway inflammation in dogs. Canine peripheral airways received DAC (delivered under general anaesthesia through a bronchoscope) every 48 h for two weeks. Peripheral airway resistance and reactivity were measured prior to each DAC. After the final DAC, bronchoalveolar lavage fluid (BALF) cells and soluble mediators from challenged and control airways were measured. Repeated bronchoscopy had no effect on airway mechanics. Repeated DAC produced cumulative increases in peripheral airway resistance and peak obstructive response to DAC. The response to hypocapnia was also increased in airways receiving repeated DAC. However, when the response to agonists was expressed as a change from baseline, consistent significant increases were not observed. Repeated bronchoscopy produced insignificant changes in BALF cells and eicosanoid mediators. Repeated DAC produced marked eosinophilic inflammation and increased prostaglandins D2, E2, and F2alpha, as well as leukotrienes C4-E4. In conclusion, repeated dry air challenge in dogs in vivo causes persistent airway obstruction and inflammation not unlike that found in human asthma. (+info)
(8/408) Priming with a secreted form of the fusion protein of respiratory syncytial virus (RSV) promotes interleukin-4 (IL-4) and IL-5 production but not pulmonary eosinophilia following RSV challenge.
The attachment (G) protein of respiratory syncytial virus (RSV) is synthesized as two mature forms: a membrane-anchored form and a smaller secreted form. BALB/c mice scarified with vaccinia virus (VV) expressing the secreted form develop a greater pulmonary eosinophilic influx following RSV challenge than do mice scarified with VV expressing the membrane-anchored form. To determine if a soluble form of an RSV protein was sufficient to induce eosinophilia following RSV challenge, a cDNA that encoded a secreted form of the fusion (F) protein of RSV was constructed and expressed in VV (VV-Ftm(-)). Splenocytes and lung lymphocytes from mice primed with VV-Ftm(-) produced significantly more of the Th2 cytokines interleukin-4 (IL-4) and IL-5 than did mice vaccinated with VV expressing either the native (membrane-anchored) form of the F protein or the G protein. Although mice scarified with VV-Ftm(-) developed a slight increase in the number of pulmonary eosinophils following RSV infection, the increase was not as great as that seen in VV-G-primed mice. Despite the increased IL-4 and IL-5 production and in contrast to mice primed with VV-G, mice primed with VV-Ftm(-) developed RSV-specific cytotoxic T lymphocytes (CTL) and maintained high levels of gamma interferon production. These data demonstrate that recombinant VV strains expressing soluble forms of RSV proteins induce immune responses that are more Th2-like. However, this change alone does not appear sufficient to induce vaccine-augmented disease in the face of active CD8(+) CTL populations. (+info)