Targeting key proximal drivers of type 2 inflammation in disease

@article{Gandhi2016TargetingKP,
  title={Targeting key proximal drivers of type 2 inflammation in disease},
  author={Namita A Gandhi and Brandy L Bennett and Neil S. Graham and Gianluca Pirozzi and Neil Stahl and George D. Yancopoulos},
  journal={Nature Reviews Drug Discovery},
  year={2016},
  volume={15},
  pages={35-50}
}
Systemic type 2 inflammation encompassing T helper 2 (TH2)-type responses is emerging as a unifying feature of both classically defined allergic diseases, such as asthma, and a range of other inflammatory diseases. Rather than reducing inflammation with broad-acting immunosuppressants or narrowly targeting downstream products of the TH2 pathway, such as immunoglobulin E (IgE), efforts to target the key proximal type 2 cytokines — interleukin-4 (IL-4), IL-5 and IL-13 — represent a promising… Expand
Understanding the key issues in the treatment of uncontrolled persistent asthma with type 2 inflammation
TLDR
Elevated levels of biomarkers downstream of type 2 cytokines, including fractional exhaled nitric oxide, serum IgE and blood and sputum eosinophils, have been linked to mechanisms involved in type 2 inflammation, and have the potential to aid diagnosis, and to predict and monitor response to treatment. Expand
Commonality of the IL-4/IL-13 pathway in atopic diseases
TLDR
Dupilumab, a human monoclonal antibody that simultaneously inhibits signaling of IL-4 and IL-13, has demonstrated significant clinical efficacy in AD, asthma, and CSwNP, suggesting that there is a common underlying pathogenic pathway, and that IL- 4 and IL -13 cytokines are central to regulating the pathogenesis of these atopic diseases. Expand
The emerging role of type 2 inflammation in asthma
TLDR
The role of Th2 cells and ILC2 in the recent new concept of type 2 inflammation is highlighted, indicating that adaptive Th2- and innate cell responses represent two integrated systems in the production of IL-4, IL-5, and IL-13 leading to the current ‘concept’ of type 1 inflammation. Expand
Dupilumab to Treat Type 2 Inflammatory Diseases in Children and Adolescents
TLDR
This review presents the most recent evidence on dupilumab for the treatment of type 2 inflammatory diseases and discusses the future perspective, focusing on the pediatric age group and adolescents. Expand
Therapeutic targeting of the IL-13 pathway in skin inflammation
TLDR
This narrative literature review is focused on the pivotal role of IL-13 in the immunopathogenesis of AD and other skin diseases and indicates the central role of Dupilumab has demonstrated in the pathogenesis ofAD, asthma, and other diseases in the atopic spectrum. Expand
T2 asthma and T2-associated diseases: a consolidated approach to biological therapy
TLDR
The article presents the results of experimental studies proving that the activation of IL-4/IL-13 can cause significant hyperresponsiveness of the human airway smooth muscles and the combined blockade of the activity of these cytokines using a human monoclonal antibody against the common IL- 4/13 receptor-subunit-dupilumab determines the clinical efficacy. Expand
The Role of Dupilumab in Severe Asthma
TLDR
An overview of the recent research in the field of respiratory medicine about dupilumab mechanism of action and its effects is provided, revealing significant improvements in lung function, asthma control, and exacerbation rate. Expand
Interleukin‐13: Targeting an underestimated cytokine in atopic dermatitis
TLDR
An update on the role of IL‐13 in AD is provided and the different strategies aimed at interfering with its biologic activity as well as their potential in a precision medicine approach in the management of AD are discussed. Expand
The Changing Landscape of Atopic Dermatitis - Focusing on JAK Inhibitors.
TLDR
The molecular basis for AD has been increasingly understood as well as for pruritus, and the cellular infiltrate of AD lesions mainly consists of CD4+ T cells, which are considered the key to chronic inflammation. Expand
Targeting the T Helper 2 Inflammatory Axis in Atopic Dermatitis
TLDR
State-of-the-art antibodies and novel small molecules currently in development may provide more consistent benefit to patients with AD by specifically targeting the immune and molecular pathways important for the pathogenesis of AD. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 177 REFERENCES
T-helper type 2-driven inflammation defines major subphenotypes of asthma.
TLDR
Asthma can be divided into at least two distinct molecular phenotypes defined by degree of Th2 inflammation, and Th2 cytokines are likely to be a relevant therapeutic target in only a subset of patients with asthma. Expand
Type 2 cytokines: mechanisms and therapeutic strategies
  • T. Wynn
  • Biology, Medicine
  • Nature Reviews Immunology
  • 2015
TLDR
The many endogenous negative regulatory mechanisms that antagonize type 2 immunity are discussed and how therapies that target some of these pathways are being developed to treat type 2-mediated disease are highlighted. Expand
Investigational therapeutics targeting the IL-4/IL-13/STAT-6 pathway for the treatment of asthma
TLDR
Current studies of compounds targeting the interleukin-4/interleuk in-13 pathway are summarised to provide a rationale for the development of such compounds for this use and provide a new therapeutic modality for patients with uncontrolled severe asthma. Expand
Cytokine-directed therapies for the treatment of chronic airway diseases.
  • P. Barnes
  • Medicine
  • Cytokine & growth factor reviews
  • 2003
TLDR
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 non-specific inhibitors may be reduced by the inhaled route. Expand
Targeting interleukin-4 in asthma: lost in translation?
TLDR
The role of IL-4 in asthma,IL-4 signaling, which is crucial in the development of allergic airway inflammation, is addressed, and an overview of preclinical and clinical studies targeting the IL- 4 Receptor pathway is given. Expand
Allergy, Asthma, and Inflammation: Which Inflammatory Cell Type Is More Important?
  • R. Moqbel, S. Odemuyiwa
  • Medicine
  • Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology
  • 2008
TLDR
It is proposed that in a complex inflammatory milieu characterizing the complex syndromes the authors call asthma, no single cell phenotype is responsible for the condition and thus should be a sole target for therapeutic strategies. Expand
IL-4 Attenuates Th1-Associated Chemokine Expression and Th1 Trafficking to Inflamed Tissues and Limits Pathogen Clearance
TLDR
IL-4 attenuates lymphocyte recruitment to the inflamed/infected dermis and limits pathogen clearance, which supports a model whereby IL-4 dampens Th1-chemokines at the site of inflammation limiting Th1 recruitment. Expand
Efficacy of soluble IL-4 receptor for the treatment of adults with asthma.
TLDR
These promising data suggest that IL-4R is safe and effective in the treatment of moderate persistent asthma. Expand
Critical Role for IL-13 in the Development of Allergen-Induced Airway Hyperreactivity1
TLDR
It is definitively demonstrate that IL-13 is necessary and sufficient for the induction of AHR and that eosinophilic airway inflammation in the absence of IL- 13 is inadequate for the induction of A HR, and treatment of human asthma with antagonists ofIL-13 may be very effective. Expand
Effects of interleukin-13 blockade on allergen-induced airway responses in mild atopic asthma.
TLDR
IL-13 has a role in allergen-induced airway responses in humans and further study is required to determine whether anti- IL-13 monoclonal antibodies will be beneficial clinically. Expand
...
1
2
3
4
5
...