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Allergic Asthmatic Patients (allergic + asthmatic_patient)

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Medical Sciences	100%

Selected Abstracts

Proinflammatory cytokines (IL-17, IL-6, IL-18 and IL-12) and Th cytokines (IFN- ,, IL-4, IL-10 and IL-13) in patients with allergic asthma

CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2001
C. K. Wong
Allergen-reactive T helper type-2 (Th2) cells and proinflammatory cytokines have been suggested to play an important role in the induction and maintenance of the inflammatory cascade in allergic asthma. We compared the plasma concentrations of novel proinflammatory cytokines IL-17 and IL-18, other proinflammatory cytokines IL-6 and IL-12, Th2 cytokines IL-10 and IL-13, and intracellular interferon- , (IFN- ,) and IL-4 in Th cells of 41 allergic asthmatics and 30 sex- and age-matched health control subjects. Plasma cytokines were measured by enzyme-linked immunosorbent assay. Intracellular cytokines were quantified by flow cytometry. Plasma IL-18, IL-12, IL-10, IL-13 concentrations were significantly higher in allergic asthmatic patients than normal control subjects (IL-18: median 228·35 versus 138·72 pg/ml, P < 0·001; IL-12: 0·00 versus 0·00 pg/ml, P = 0·001; IL-10: 2·51 versus 0·05 pg/ml, P < 0·034; IL-13: 119·38 versus 17·89 pg/ml, P < 0·001). Allergic asthmatic patients showed higher plasma IL-17 and IL-6 concentrations than normal controls (22·40 versus 11·86 pg/ml and 3·42 versus 0·61 pg/ml, respectively), although the differences were not statistically significant (P = 0·077 and 0·053, respectively). The percentage of IFN- , -producing Th cells was significantly higher in normal control subjects than asthmatic patients (23·46 versus 5·72%, P < 0·001) but the percentage of IL-4 producing Th cells did not differ (0·72 versus 0·79%, P > 0·05). Consequently, the Th1/Th2 cell ratio was significantly higher in normal subjects than asthmatic patients (29·6 versus 8·38%, P < 0·001). We propose that allergic asthma is characterized by an elevation of both proinflammatory and Th2 cytokines. The significantly lower ratio of Th1/Th2 cells confirms a predominance of Th2 cells response in allergic asthma. [source]

Blockade of CCR4 in a humanized model of asthma reveals a critical role for DC-derived CCL17 and CCL22 in attracting Th2 cells and inducing airway inflammation

ALLERGY, Issue 7 2009
F. Perros
Background:, As Th2 type lymphocytes orchestrate the cardinal features of allergic asthma, inhibiting their recruitment to the lungs could be of therapeutic benefit. Although human Th2 cells express the CCR4 chemokine receptor and increased production of CCR4 ligands has been found in asthmatic airways, studies in animals have reached contradictory conclusions on whether blocking this pathway would be beneficial. Objective:, As a lack of efficacy might be due to differences between mouse and man, we readdressed this question using a humanized severe combined immunodeficiency model of asthma. Methods:, Mice received peripheral blood mononuclear cells from house dust mite (HDM) allergic asthmatic patients and then underwent bronchial challenge with HDM. Results:, This resulted in marked allergic inflammation and bronchial hyper-reactivity. Administration of CCR4 blocking antibody abolished the airway eosinophilia, goblet cell hyperplasia, IgE synthesis and bronchial hyperreactivity. In this chimeric system, human CD11c+ dendritic cells (DCs) were the predominant source of CCR4 ligands, suggesting that DC-derived chemokines attract Th2 cells. In separate experiments using human DCs, in vitro exposure to HDM of DCs from HDM allergic patients but not healthy controls caused CCL17 and CCL22 release that resulted in chemoattraction of polarized human Th2 cells in a CCR4-dependent way. Conclusions:, Taken together, our data provide proof of concept that CCR4 blockade inhibits the salient features of asthma and justify further clinical development of CCR4 antagonists for this disease. [source]

Impaired virus-induced interferon-,2 release in adult asthmatic patients

CLINICAL & EXPERIMENTAL ALLERGY, Issue 3 2006
K. Gehlhar
Summary Background Interferon-, (IFN-,) not only serves as a first defence line of the immune system against viral attacks but also interacts with T-helper type 1 (Th1)/ T-helper type 2 (Th2) regulation and various other cell types like basophils and monocytes, thereby linking innate and acquired immunity. Recently, we demonstrated that children with allergic asthma produced significantly lower amounts of virus-induced IFN-,2 compared with healthy children or those with intrinsic asthma. Objective In this study, we extend our analysis to examine in a cohort study whether IFN-,2 is also reduced in allergic asthma of adults. Methods Adults with allergic asthma and healthy controls were prospectively recruited. Blood cultures were stimulated with different viruses (respiratory syncytial virus (RSV), newcastle disease virus (NDV)) and analysed for IFN-,2 protein release and gene transcription. Results Virus-induced IFN-,2 release from blood cells of allergic asthmatic patients was significantly reduced compared with healthy controls, independent of the virus used (NDVasthma=221±134 pg/mL, NDVhealthy=555±341 pg/mL, P=0.003 and RSVasthma=46±27 pg/mL, RSVhealthy=108±90 pg/mL, P=0.014). Values=mean±standard deviation). It was not influenced by medication, especially cortico-steroids. IFN-,2 mRNA expression 5 h after NDV stimulation confirmed the ELISA results and correlated well with release data (r=0.397, P=0.033). Conclusion Like children, adults with allergic asthma show impaired virus-induced IFN-,2 release in whole blood, indicating a systemic phenomenon in patients with bronchial asthma and atopic phenotype. Impaired virus-induced IFN-, release could be a marker of inflammation in chronic allergic asthma. [source]

The NK-2 receptor antagonist SR 48968C does not improve adenosine hyperresponsiveness and airway obstruction in allergic asthma

CLINICAL & EXPERIMENTAL ALLERGY, Issue 2 2001
J. Kraan
When stimulated, excitatory nonadrenergic noncholinergic (e-NANC) nerves locally release tachykinins like Neurokinin (NK) A and Substance P, causing neurogenic inflammation and airway obstruction via activation of specific NK-1 and NK-2 receptors. The recently developed nonpeptide NK-2 receptor antagonist SR 48968C has a high affinity for the NK-2 receptor, and is a strong and selective antagonist of NK-2 receptor mediated airway obstruction. In a placebo-controlled cross-over study, we investigated the effect of SR 48968C, administrated orally once-daily in a dosage of 100 mg during 9 days, on airway responsiveness to adenosine 5,-monophosphate (AMP) in 12 allergic asthmatic patients. Furthermore, we assessed its effect on airway obstruction, by measuring FEV1 on the first and last day of each treatment period and by peak flow registration at home throughout the study period. SR 48968C had no significant effect on PC20AMP or on FEV1 measured on day 1 and 9, and morning and evening peakflow measured at home on day 2,8. Thus, although SR 48968C was administrated in a dosage that might cause a demonstrable blocking effect on airway NK-2 receptors in asthma, it did not have a significant bronchodilatory or bronchoprotective effect against adenosine hyperresponsiveness in this study. Further studies are needed to assess the value of SR 48968C and other NK receptor antagonists in the treatment of asthma [source]