Effect of suplatast tosilate, a Th2 cytokine inhibitor, on steroid-dependent asthma: a double-blind randomised study

Tamaoki, Jun; Kondo, Mitsuko; Sakai, Naotaka; Tagaya, Etsuko; Nakata, Junko; Isono, Kazuo; Nagai, Atsushi; Aoshiba, Kazutetsu

doi:10.1016/s0140-6736(00)02501-0

Cited by 123 publications

(68 citation statements)

References 20 publications

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“…Several studies have documented increased numbers of activated CD4+ T-cells in the lungs of subjects with asthma, and, in the majority of studies to date these cells were found to express cytokines or transcription factors characteristic of Th2 cells [22][23][24][25][26][27][28][29][30][31][32]. In some studies this apparent Th2 bias in asthma extends outside of the airway to circulating lymphocytes [33][34][35].…”

Section: Th2 Cells Asthma and Atopymentioning

confidence: 99%

T-helper cell type-2 regulation in allergic disease

Georas

Guo

Fanis

et al. 2005

European Respiratory Journal

150

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Substantial experimental evidence now supports the notion that allergic diseases are characterised by a skewing of the immune system towards a T-helper cell type-2 (Th2) phenotype.Studies using both human and mouse model systems have provided key evidence for the role that Th2 cytokines play in driving many of the hallmarks of allergic inflammation. Furthermore, the signalling pathways by which Th2 cytokines exert their effects on airway target cells are rapidly being elucidated, and antagonists of the Th2 pathway are under active development.In this review, the current knowledge of the role of T-helper cell type-2 cells in asthma is summarised, focusing on how and where T-helper cell type-2 cells differentiate from naïve precursors. The signalling molecules and transcription factors involved in T-helper cell type-2 differentiation will be reviewed in detail, in an attempt to translate studies using genetically modified mice into meaningful insights about asthma and other allergic diseases.

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Section: Th2 Cells Asthma and Atopymentioning

confidence: 99%

T-helper cell type-2 regulation in allergic disease

Georas

Guo

Fanis

et al. 2005

European Respiratory Journal

150

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“…More selective Th2-selective drugs may be safer for the treatment of asthma in the future. An inhibitor of Th2-derived cytokines, suplatast tosilate [94], is reported to provide clinical benefit in asthma [95]. Cytotoxic (CD8z) T-lymphocytes are prominent in COPD and therefore immunomodulatory drugs may also have a role in this disease.…”

Section: Immunomodulatory Drugsmentioning

confidence: 99%

Cytokine modulators as novel therapies for airway disease

Barnes¹

2001

European Respiratory Journal

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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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“…In adults with asthma, suplatast tosilate shows comparable anti-inflammatory activity to inhaled steroids (16), as well as improving lung function, asthma symptoms, and airway hyperresponsiveness (16,17). In patients receiving high-dose inhaled steroids, addition of suplatast tosilate allows the steroid dose to be reduced (18). Furthermore, evaluation by bronchial biopsy has shown that this drug decreases the number of eosinophils and EG2-positive cells in the airway mucosa, as well as inhibiting goblet cell hyperplasia (17,19).…”

Section: Th2 Cytokine Inhibitor: Suplatast Tosilatementioning

confidence: 99%