Biology of interleukin‐5 and its relevance to allergic disease

Egan, Robert W.; Umland, Shelby P.; Cuss, Francis M.; Chapman, Richard W.

doi:10.1111/j.1398-9995.1996.tb04561.x

Cited by 85 publications

(27 citation statements)

References 137 publications

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“…Th2 cytokines can account directly or indirectly for the majority of pathophysiological manifestations. For example, IL-4 and IL-13 are the switch factors for B cell production of IgE; IL-5 is a growth and differentiation factor for eosinophils (32,33). The present study clearly demonstrates that FTY720 not only inhibits the Th2 cell-mediated eosinophilic inflammation but is also active in a relevant disease model using active sensitization and challenge to allergen, which besides allergen-specific Th2 cells also involves allergen-specific IgE and subsequent allergen-mediated mast cell degranulation events.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Th1- and Th2-Mediated Airway Inflammation by the Sphingosine 1-Phosphate Receptor Agonist FTY720

Sawicka

Zuany-Amorim

Manlius

et al. 2003

The Journal of Immunology

133

114

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The sphingosine 1-phosphate receptor agonist FTY720 is a novel immunomodulator that sequesters lymphocytes in secondary lymphoid organs and thereby prevents their migration to sites of inflammation. However, there is currently no information available on whether this drug affects Th1 or Th2 cell-mediated lung-inflammatory responses. The effect of FTY720 was therefore investigated in a murine airway inflammation model using OVA-specific, in vitro differentiated, and adoptively transferred Th1 and Th2 cells. Both Th1 and Th2 cells express a similar pattern of FTY720-targeted sphingosine 1-phosphate receptors. The OVA-induced Th1-mediated airway inflammation characterized by increased numbers of lymphocytes and neutrophils in bronchoalveolar lavage fluid was significantly inhibited by oral FTY720 treatment. Similarly, FTY720 suppressed the Th2 cell-induced bronchoalveolar lavage fluid eosinophilia and the infiltration of T lymphocytes and eosinophils into the bronchial tissue. Moreover, the Ag-induced bronchial hyperresponsiveness to inhaled metacholine was almost completely blocked. The inhibitory effect of FTY720 on airway inflammation, induction of bronchial hyperresponsiveness, and goblet cell hyperplasia could be confirmed in an actively Ag-sensitized murine asthma model, clearly indicating that Th2 cell-driven allergic diseases such as asthma could benefit from such treatment.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Th1- and Th2-Mediated Airway Inflammation by the Sphingosine 1-Phosphate Receptor Agonist FTY720

Sawicka

Zuany-Amorim

Manlius

et al. 2003

The Journal of Immunology

133

114

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“…In fact, anti-IgE therapy with a recombinant humanized monoclonal antibody reduces the incidence of asthma exacerbations even after inhaled corticosteroids are markedly reduced or completely withdrawn (de Amato, 2003;Ruffin and Busch, 2004). On the other hand, IL-5 is crucial in orchestrating eosinophilic inflammation in asthma (Egan et al, 1996). It was shown that blocking antibodies to IL-5 inhibits eosinophilic inflammation and airway hyperresponsiveness in animal models of asthma (Hamelmann et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

JTP-27536 [(+)-1,3-Dihydroxy-2-hydroxymethylpropyl-2-ammonium 2-[(R)-3-Cyclo-hexyl-1-phenylpropyl]-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carboxylate Monohydrate], a Novel Inhibitor of Immunoglobulins and Interleukin-5 with Anti-Inflammatory Properties in Mouse Allergic Dermatitis Model

Mimura¹,

Shinozaki²,

Kawasaki³

et al. 2005

J Pharmacol Exp Ther

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We report a novel synthetic compound JTP-27536 [(ϩ)-1,3-dihydroxy-2-hydroxymethylpropyl-2-ammonium 2-[(R)-3-cyclohexyl-1-phenylpropyl]-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carboxylate monohydrate] as an inhibitor of immunoglobulins (Igs) and interleukin (IL)-5 production in vitro and in vivo. JTP-27536 inhibited IgE production in mouse and human B cells with IC 50 values of 2.5 and 2.1 M, respectively, and the inhibition was stronger than that on IgG1 and IgM production (IC 50 Ͼ 10 M). JTP-27536 also inhibited IL-5 production in mouse splenocytes and human peripheral blood mononuclear cells with IC 50 values of 3.3 and 1.3 M, respectively, without affecting mouse interferon (IFN)-␥, IL-2, IL-4, IL-10, or human IL-4 production. In contrast, prednisolone not only inhibited mouse IgE production but also mouse IFN-␥, IL-2, IL-4, and IL-10 and human IL-4 and IL-5 production in vitro. The effect of suplatast tosilate, a Th2 cytokine inhibitor, on antibody and cytokine production was less potent than that of JTP-27536. In vivo animal experiments using dinitrophenylated ascarissensitized mice and 2,4,6-trinitro-1-chrolobenzene-induced chronic dermatitis mice showed that JTP-27536 was more potent than suplatast tosilate and comparable with prednisolone in inhibiting ear swelling, antigen-specific IgE and IL-5 production, and cell infiltrations into the inflamed tissue. These results indicate that JTP-27536 is an inhibitor of Igs, in particular IgE, and of IL-5, which has antiallergic properties in mouse dermatitis model, and suggest that an inhibitor of Igs and IL-5 like JTP-27536 may be useful as a drug for the treatment of allergic diseases.

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“…Interleukin (IL)-5 plays an essential role in orchestrating the eosinophilic inflammation of asthma [12,13]. In IL-5 gene knockout mice, the eosinophilic response to allergen and the subsequent airway hyperresponsiveness (AHR) are markedly suppressed, validating the strategy of inhibiting IL-5 ( fig.…”

Section: Anti-interleukin-5mentioning

confidence: 99%

Cytokine modulators as novel therapies for airway disease

Barnes¹

2001

Eur Respir J

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Cytokine modulators as novel therapies for airway disease. P.J. Barnes. #ERS Journals Ltd 2001. ABSTRACT: Cytokines play a critical role in orchestrating and perpetuating inflammation in asthma and chronic obstructive pulmonary disease (COPD), and several specific cytokine and chemokine inhibitors are now in development for the future therapy of these diseases.Anti-interleukin (IL)-5 is very effective at reducing peripheral blood and airway eosinophil numbers, but does not appear to be effective against symptomatic asthma. Inhibition of IL-4 with soluble IL-4 receptors has shown promising early results in asthma. Inhibitory cytokines, such as IL-10, interferons and IL-12 are less promising, as systemic delivery causes side-effects. Inhibition of tumour necrosis factor-a may be useful in severe asthma and for treating severe COPD with systemic features.Many chemokines are involved in the inflammatory response of asthma and COPD and several low-molecular-weight inhibitors of chemokine receptors are in development. CCR3 antagonists (which block eosinophil chemotaxis) and CXCR2 antagonists (which block neutrophil and monocyte chemotaxis) are in clinical development for the treatment of asthma and COPD respectively.Because so many cytokines are involved in asthma, drugs that inhibit the synthesis of multiple cytokines may prove to be more useful; several such classes of drug are now in clinical development and any risk of side-effects with these nonspecific inhibitors may be reduced by the use of inhalational route of delivery.

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Biology of interleukin‐5 and its relevance to allergic disease

Cited by 85 publications

References 137 publications

Inhibition of Th1- and Th2-Mediated Airway Inflammation by the Sphingosine 1-Phosphate Receptor Agonist FTY720

Inhibition of Th1- and Th2-Mediated Airway Inflammation by the Sphingosine 1-Phosphate Receptor Agonist FTY720

JTP-27536 [(+)-1,3-Dihydroxy-2-hydroxymethylpropyl-2-ammonium 2-[(R)-3-Cyclo-hexyl-1-phenylpropyl]-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carboxylate Monohydrate], a Novel Inhibitor of Immunoglobulins and Interleukin-5 with Anti-Inflammatory Properties in Mouse Allergic Dermatitis Model

Cytokine modulators as novel therapies for airway disease

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