Interleukin 4, but not interleukin 5 or eosinophils, is required in a murine model of acute airway hyperreactivity.

Corry, David B.; Folkesson, Hans G.; Warnock, Martha L.; Erle, David J.; Matthay, Michael A.; Wiener-Kronish, Jeanine P.; Locksley, Richard M.

doi:10.1084/jem.183.1.109

Cited by 700 publications

(525 citation statements)

References 52 publications

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“…Fig. 2 shows that the OVA-sensitized and challenged wild-type mice developed significant AHR compared with OVA-sensitized, PBS-challenged wild-type mice ( p Ͻ 0.05), consistent with other investigators (11,12). The baseline airway reactivities of OVA-sensitized and PBS-challenged IL-5 TG mice and similarly treated wild-type mice were nearly identical.…”

Section: Effects Of Airway Eosinophilia On Bronchial Reactivitysupporting

confidence: 86%

“…In mice neutralization of IL-5 prevented allergen-induced AHR (9), and overproduction of IL-5 in the airways led to AHR (10). However, previous results, suggesting that AHR was prevented in IL-5 knockout mice (11), but was not prevented in mice treated with anti-IL-5 mAb, were conflicting (12). Furthermore, mice treated with anti-IL-5 mAb showed less eosinophilia, but retained their AHR (13,14).…”

Section: Marked Airway Eosinophilia Prevents Development Of Airwaymentioning

confidence: 92%

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Marked Airway Eosinophilia Prevents Development of Airway Hyper-responsiveness During an Allergic Response in IL-5 Transgenic Mice

Kobayashi

Izutsu

Kita

2003

The Journal of Immunology

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Tissue eosinophilia probably plays important roles in the pathophysiology of bronchial asthma and allergic disorders; however, this concept was challenged recently by controversial results in mouse models of bronchial asthma treated with anti-IL-5 Ab and the failure of anti-IL-5 therapy in humans. We have now used a unique model, IL-5 transgenic (TG) mice, to address a fundamental question: is airway eosinophilia beneficial or detrimental in the allergic response? After sensitization and challenge with OVA, IL-5 TG mice showed a marked airway eosinophilia. Surprisingly, these IL-5 TG mice showed lower airway reactivity to methacholine. Immunohistochemical analysis of the lungs revealed a marked peribronchial infiltration of eosinophils, but no eosinophil degranulation. In vitro, mouse eosinophils from peritoneal lavage fluids did not produce superoxide anion, but did produce an anti-inflammatory and fibrotic cytokine, TGF-β1. Indeed, the TGF-β1 levels in bronchoalveolar lavage fluid specimens from IL-5 TG mice directly correlated with airway eosinophilia (r = 0.755). Furthermore, anti-IL-5 treatment of IL-5 TG mice decreased both airway eosinophilia and TGF-β1 levels in bronchoalveolar lavage fluids and increased airway reactivity. Thus, in mice, marked eosinophilia prevents the development of airway hyper-reactivity during an allergic response. Overall, the roles of eosinophils in asthma and in animal models need to be addressed carefully for their potentially detrimental and beneficial effects.

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Section: Effects Of Airway Eosinophilia On Bronchial Reactivitysupporting

confidence: 86%

Section: Marked Airway Eosinophilia Prevents Development Of Airwaymentioning

confidence: 92%

Marked Airway Eosinophilia Prevents Development of Airway Hyper-responsiveness During an Allergic Response in IL-5 Transgenic Mice

Kobayashi

Izutsu

Kita

2003

The Journal of Immunology

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“…Presently, the participation of eosinophils in the development of AHR is not clear. Studies by Nagai et al (14) and Corry et al (43) showed that the anti-IL-5 Ab treatment inhibited airway eosinophilia, but not AHR. Kobayashi Wild-type and Fc⑀RI␣ Ϫ/Ϫ mice were sensitized to OVA in alum on days 1 and 14.…”

Section: Discussionmentioning

confidence: 98%

IgE-Dependent Mast Cell Activation Potentiates Airway Responses in Murine Asthma Models

Mayr

Zuberi

Zhang

et al. 2002

The Journal of Immunology

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We have studied murine models of asthma using FcεRIα-chain-deficient (FcεRIα−/−) mice to investigate the role of IgE-dependent mast cell activation in these models. When mice were either 1) immunized once with OVA in alum i.p. and then challenged with OVA intranasally, or 2) repeatedly immunized with OVA in the absence of adjuvant and subsequently challenged with nebulized OVA, FcεRα−/− mice had significantly fewer eosinophils and lower IL-4 levels in their bronchoalveolar lavage fluid compared with wild-type mice. When mice were given anti-IL-5 antibody before OVA challenge in protocol 1, eosinophilic infiltration into the airways was significantly suppressed in both genotypes, but only FcεRIα−/− mice showed significantly reduced airway hyperresponsiveness (AHR). In addition, when mice immunized and challenged with OVA also received a late OVA provocation at a higher concentration and were then exposed to methacholine, only wild-type mice developed a substantial increase in AHR. Since FcεRI is expressed mainly on mast cells in mouse airways, we conclude that IgE-dependent activation of this cell type plays an important role in the development of allergic airway inflammation and AHR in mice. The models used may be of value for testing inhibitors of IgE or mast cells for development of therapeutic agents for human asthma.

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“…Several studies indicate the existence of a mechanism dependent on IL-5 and eosinophils that induce pulmonary damage and intensify AHR [3][4][5]. In other studies, however, the induction of AHR was observed despite the absence of infiltrating eosinophils, suggesting dissociation between these phenomena [6][7][8][9][10]. Macrophage migration inhibitory factor (MIF) is a pleiotropic molecule and critical mediator of innate and acquired immune responses [11,12].…”

Section: Introductionmentioning

confidence: 99%

Macrophage migration inhibitory factor is essential for allergic asthma but not for Th2 differentiation

et al. 2007

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Macrophage migration inhibitory factor (MIF) is increased in asthmatic patients and plays a critical role in the pathogenesis of asthma. We show here that mice lacking MIF failed to develop airway hyper-responsiveness (AHR), tissue eosinophilia, and mucus metaplasia. Analysis of the bronchoalveolar fluids revealed a substantial reduction of IL-13, eotaxin and cysteinyl-leukotrienes. The lack of these cardinal features of asthma in MIF -/-mice occurs regardless of high concentrations of IL-4 in the lung and OVAspecific IgE in the serum. Antigen-specific lymphocyte proliferation and IL-13 production were similarly increased in the draining lymph nodes of OVA-immunized and challenged MIF -/-mice compared to WT, but were reduced in the spleen of MIF -/-, thus indicating differential roles of MIF in these compartments. Stimulation of naive CD4 + cells with anti-CD3 antibody demonstrated that MIF -/-cells produced increased amounts of IFN-c and IL-4 compared to WT CD4 + cells. Finally, treatment of sensitized BALB/c mice with neutralizing anti-MIF antibody abrogated the development of ARH and airway inflammation without affecting the production of Th2 cytokines or IgE. The present study demonstrates that MIF is required for allergic inflammation, adding important elements to our knowledge of asthma pathogenesis and suggesting that neutralization of MIF might be of therapeutic value in asthma. IntroductionAllergic asthma is a disorder characterized by chronic lung inflammation, reversible airway obstruction and increases in airway hyper-responsiveness (AHR) to nonspecific stimuli. Several studies have provided compelling evidences that the lung infiltrating leukocytes and the proinflammatory mediators they produce initiate cellular damage, amplify the immune response, cause airway physiological changes and tissue remodeling [1]. The airway inflammation of asthma has a predominance of Th2 CD4 + lymphocytes, eosinophils and mast cells infiltrating the lung interstitium. Several studies indicate the existence of a mechanism dependent on IL-5 and eosinophils that induce pulmonary damage and intensify AHR [3][4][5]. In other studies, however, the induction of AHR was observed despite the absence of infiltrating eosinophils, suggesting dissociation between these phenomena [6][7][8][9][10]. Macrophage migration inhibitory factor (MIF) is a pleiotropic molecule and critical mediator of innate and acquired immune responses [11,12]. Pre-formed MIF protein is present in many cell types and is released in response to different stimuli, such as infection and cytokine stimulation [12]. MIF exhibits several proinflammatory functions, including the induction of TNF-a, IL-1 and NO release from macrophages, and the production of arachidonic acid and eicosanoids through the induction of phospholipase A 2 and cyclooxygenase [13,14]. A unique property of MIF is its secretion by immune cells in response to physiological increase in glucocorticoid levels. Once released, MIF can counterregulate the anti-inflammatory effects of steroids on cyt...

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Interleukin 4, but not interleukin 5 or eosinophils, is required in a murine model of acute airway hyperreactivity.

Cited by 700 publications

References 52 publications

Marked Airway Eosinophilia Prevents Development of Airway Hyper-responsiveness During an Allergic Response in IL-5 Transgenic Mice

Marked Airway Eosinophilia Prevents Development of Airway Hyper-responsiveness During an Allergic Response in IL-5 Transgenic Mice

IgE-Dependent Mast Cell Activation Potentiates Airway Responses in Murine Asthma Models

Macrophage migration inhibitory factor is essential for allergic asthma but not for Th2 differentiation

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