Inhibition of Allergen-Induced IgE and IgG1 Production by Soluble IL-4 Receptor

Renz, Harald; Enssle, Karl-Heinz; Lauffer, Leander; Kurrle, R.; Gelfand, Erwin W.

doi:10.1159/000236889

Cited by 79 publications

(49 citation statements)

References 16 publications

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“…A limited number of animal models of allergy are based on aeroallergens present in daily environment such ragweed (17). Although the majority of asthmatic patients is sensitized with mites, very few investigators used mites or mite extracts as immunizing agents (9,15,16).…”

Section: Introductionmentioning

confidence: 99%

Shortening of the Induction Period of Allergic Asthma in Cynomolgus Monkeys by Ascaris suum and House Dust Mite

et al. 2008

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Abstract. The development of non-human primate models of asthma requires a period of time (e.g., 0.5 -1 year). To develop the models in a short period, male cynomolgus monkeys were sensitized with dinitrophenyl-Ascaris suum (DNP-As) allergen by intraperitoneal and intramuscular injection and by intratracheal inhalation. All sensitized animals developed positive intradermal skin reaction to DNP-As. Sensitization elevated allergen-specific IgE levels in serum, the number of CCR4-positive T helper lymphocytes in peripheral blood, and IL-4 and IL-5 releases from phorbol 12-myristate 13-acetate-and ionomycin-stimulated peripheral blood. In addition, allergen challenge induced increases in lung resistance, airway inflammation, and hyperresponsiveness to inhaled methacholine. Next, animals were sensitized with house dust mite extracts (HDM) under the similar procedure. In these animals sensitized with DNP-As or HDM, inhaled fluticasone propionate and oral prednisolone inhibited the allergen-induced airway hyperresponsiveness. Taken together, monkey asthma models were successfully developed by sensitization with DNP-As or HDM under a short-term protocol (within 7 weeks). These models should be useful for the evaluation of anti-inflammatory drugs for asthma treatment.

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Section: Introductionmentioning

confidence: 99%

Shortening of the Induction Period of Allergic Asthma in Cynomolgus Monkeys by Ascaris suum and House Dust Mite

et al. 2008

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“…A small number of primate studies have used clinically meaningful aeroallergens, such as ragweed [11] or house dust mite (HDM) delivered in aerosol form [6,12,13]. PLOPPER and HYDE [3] addressed the validity of these models at the anatomical and cellular levels, and ZOU et al [14] documented changes in gene expression by microarray profiling following acute challenge with allergen.…”

mentioning

confidence: 99%

Modelling asthma in macaques: longitudinal changes in cellular and molecular markers

Ayanoglu¹,

Desai²,

Fick³

et al. 2010

Eur Respir J

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The aim of the present study was to determine whether systemic sensitisation and chronic aeroallergen challenge in macaques replicate the classical and emerging immunology and molecular pathology of human asthma.Macaques were immunised and periodically challenged over 2 yrs with house dust mite allergen. At key time-points, serum, bronchoalveolar lavage (BAL) and bronchial biopsies were assayed for genes, proteins and lymphocyte subpopulations relevant to clinical asthma.Immunisation and periodic airway challenge induced changes in immunoglobulin E, airway physiology and eosinophilia consistent with chronic, dual-phase asthma. Sensitisation increased interleukin (IL)-1b and -6 concentrations in serum, and IL-13 expression in BAL cells. Airway challenge increased: early expression of IL-5, -6, -13 and -19, and eotaxin; and variable late-phase expression of IL-4, -5 and -13, and thymus-and activation-regulated chemokine in BAL cells. CD4+ lymphocytes comprised 30% of the CD3+ cells in BAL, increasing to 50% in the late phase. Natural killer T-cells represented ,3% of the CD3+ cells. Corticosteroid treatment reduced serum histamine levels, percentage of CD4+ cells and monocyte-derived chemokine expression, while increasing CD3+ and CD8+ cells in BAL.Sensitisation and periodic aeroallergen challenge of cynomolgus macaques results in physiological, cellular, molecular and protein phenotypes, and therapeutic responses observed in human asthma, providing a model system useful in target and biomarker discovery, and translational asthma research.KEYWORDS: Asthma, corticosteroid treatment, natural killer T-cell, primate model A sthma continues to present a significant unmet medical need [1] and the search for effective asthma drugs with novel mechanisms of action continues. Nonhuman primate models most closely replicate the genetics, physiology, immunology and pathology of the human disease [2][3][4]. The availability of these models uniquely allows examination of both induction of chronic allergy-driven airway inflammation and bronchoconstriction in a controlled setting, as well as identification of key mediators for the maintenance of chronic asthma. Additionally, these models provide a platform to assess pre-clinical safety, and proof of activity and efficacy for novel asthma therapeutics, under conditions that are observed in human patients.Models of asthma have been developed in a variety of common laboratory animals, including guinea pigs, rabbits, rats, mice, sheep, cats, dogs and macaques (see review by BICE et al.[5]).However, there are significant differences in airway architecture and immune responses to chronic allergen between species. Few species develop spontaneous allergic sensitivity to allergens, chronic or prolonged immune and inflammatory responses following pulmonary allergen exposure, progressive worsening of airway responses with repeated antigen challenge, and significant accumulation of lymphoid cells outside the bronchial-associated lymphoid tissue. Murine models have been instrumental ...

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“…These studies are somewhat limited as humans are often sensitised to more than one allergen which makes it more difficult to determine the precise role of IgG in atopic asthma. The role of IgG in atopic asthma has been more extensively studied using murine models (Nakanishi et al, 1995;Renz et al, 1995;Blaser, 1996;Oshiba et al, 1996;Ravetch & Bolland, 2001;Crosby et al, 2002;Lange et al, 2002;Sehra et al, 2003;Matsui et al, 2004;Strait et al, 2006). A question arising from these studies is the relative contribution of antibody isotype to allergen handling by DC and the contribution of this to the pathogenesis of allergic airways disease.…”

Section: A Role For Antibody?mentioning

confidence: 99%

The role of dendritic cells and regulatory T cells in the regulation of allergic asthma

Burchell

Strickland

Stumbles

2010

Pharmacology & Therapeutics

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Airways hyperresponsiveness (AHR) is one of the major clinical features of allergic airways disease including allergic asthma, however the immunological mechanisms leading to the induction and regulation of this disorder are not fully understood. In this review we will summarise the evidence of a number of studies, principally in murine models of AHR, suggesting a central role for respiratory tract dendritic cells (RTDC) in the induction of AHR through the generation of lung-homing, allergen-specific effector T cells. We will also summarise the evidence supporting a role for regulatory T cells in the attenuation of AHR and will propose that, as a counterpoint to their capacity to induce AHR, RTDC may also play a role in the attenuation of AHR through the generation of regulatory T cells (Treg). A better understanding of the relationship between the physiological and immunological responses to allergen-induced AHR attenuation, and particularly the role of RTDC and Treg in this process, will be essential for the development of new treatments and therapies.

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Inhibition of Allergen-Induced IgE and IgG1 Production by Soluble IL-4 Receptor

Cited by 79 publications

References 16 publications

Shortening of the Induction Period of Allergic Asthma in Cynomolgus Monkeys by Ascaris suum and House Dust Mite

Shortening of the Induction Period of Allergic Asthma in Cynomolgus Monkeys by Ascaris suum and House Dust Mite

Modelling asthma in macaques: longitudinal changes in cellular and molecular markers

The role of dendritic cells and regulatory T cells in the regulation of allergic asthma

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