Abstract:This review examines recent articles on the relationship of cytokines to allergy and inflammation with particular emphasis on interleukin (IL)-4. The objective of this article is therefore to review published studies to identify cytokines consistently involved in allergic inflammation. Proinflammatory cytokines, including IL-4, IL-5, IL-13 and GM-CSF along with TNF-alpha play a role in allergen-induced airway leukocyte recruitment and these cytokines can be generated by T mast cells and other cells. In additio… Show more
“…Interleukin‐4 and IL‐13 are of particular interest in asthma based upon the ability of these two cytokines to drive Th2 (IL‐4) cell differentiation and activation, to enhance inflammatory responses by upregulating Vascular cell adhesion protein 1 (in concert with TNFα) involved in eosinophil and basophil recruitment (IL‐4 and IL‐13) and to prime inflammatory cells for secretion of mediators (IL‐4 and IL‐13) . Interleukin‐4 and especially IL‐13 also drive aspects of airway remodelling, including mucous metaplasia, fibroblast activation and smooth muscle development .…”
Section: Mechanism‐directed Treatment Of Asthmamentioning
While asthma is a chronic inflammatory disorder that is managed with inhaled controller and reliever drugs, there remains a large unmet need at the severe end of the disease spectrum. Here, a novel stratified approach to its treatment is reviewed, based upon identification of causal pathways, with a focus on biologics. A systematic search of the literature was made using Medline, and publications were selected on the basis of their relevance to the topic. Despite strong preclinical data for many of the more recently identified asthma targets, especially those relating to the T-helper 2 allergic pathway, clinical trials with specific biologics in moderate to severe asthma as a group have been disappointing. However, subgroup analyses based upon pathway-specific biomarkers suggest specific endotypes that are responsive. Application of hypothesis-free analytical approaches (the 'omics') to well-defined phenotypes is leading to the stratification of asthma along causal pathways. Refinement of this approach is likely to be the future for diagnosing and treating this group of diseases, as well as helping to define new causal pathways. The identification of responders and nonresponders to targeted asthma treatments provides a new way of looking at asthma diagnosis and management, especially with biologics that are costly. The identification of novel biomarkers linked to well-phenotyped patients provides a stratified approach to disease management beyond simple disease severity and involving causal pathways. In order to achieve this effectively, a closer interaction will be required between industry (therapeutic and diagnostic), academia and health workers.
“…Interleukin‐4 and IL‐13 are of particular interest in asthma based upon the ability of these two cytokines to drive Th2 (IL‐4) cell differentiation and activation, to enhance inflammatory responses by upregulating Vascular cell adhesion protein 1 (in concert with TNFα) involved in eosinophil and basophil recruitment (IL‐4 and IL‐13) and to prime inflammatory cells for secretion of mediators (IL‐4 and IL‐13) . Interleukin‐4 and especially IL‐13 also drive aspects of airway remodelling, including mucous metaplasia, fibroblast activation and smooth muscle development .…”
Section: Mechanism‐directed Treatment Of Asthmamentioning
While asthma is a chronic inflammatory disorder that is managed with inhaled controller and reliever drugs, there remains a large unmet need at the severe end of the disease spectrum. Here, a novel stratified approach to its treatment is reviewed, based upon identification of causal pathways, with a focus on biologics. A systematic search of the literature was made using Medline, and publications were selected on the basis of their relevance to the topic. Despite strong preclinical data for many of the more recently identified asthma targets, especially those relating to the T-helper 2 allergic pathway, clinical trials with specific biologics in moderate to severe asthma as a group have been disappointing. However, subgroup analyses based upon pathway-specific biomarkers suggest specific endotypes that are responsive. Application of hypothesis-free analytical approaches (the 'omics') to well-defined phenotypes is leading to the stratification of asthma along causal pathways. Refinement of this approach is likely to be the future for diagnosing and treating this group of diseases, as well as helping to define new causal pathways. The identification of responders and nonresponders to targeted asthma treatments provides a new way of looking at asthma diagnosis and management, especially with biologics that are costly. The identification of novel biomarkers linked to well-phenotyped patients provides a stratified approach to disease management beyond simple disease severity and involving causal pathways. In order to achieve this effectively, a closer interaction will be required between industry (therapeutic and diagnostic), academia and health workers.
“…IL-4 is primarily responsible for the development of Th2-type immune responses. In contrast, IFN-g, a Th1 cytokine, inhibits Th2 immune responses and may provide some rationale for the outcome of allergic airway inflammation (Saggini et al, 2011). These results demonstrate that quercetin is able to modulate Th1/Th2 cytokine production and consequently asthma pathology.…”
Section: Potential Effects Of Quercetin On Asthmamentioning
Allergic asthma is a complex inflammatory disorder characterized by airway hyperresponsiveness, eosinophilic inflammation and hypersecretion of mucus. Current therapies include β 2 -agonists, cysteinyl leukotriene receptor 1 antagonists and corticosteroids. Although these drugs demonstrate beneficial effects, their adverse side effects limit their long-term use. Thus, the development of new compounds with similar therapeutic activities and reduced side effects is both desirable and necessary. Natural compounds are used in some current therapies, as plant-derived metabolites can relieve disease symptoms in the same manner as allopathic medicines. Quercetin is a flavonoid that is naturally found in many fruits and vegetables and has been shown to exert multiple biological effects in experimental models, including the reduction of major symptoms of asthma: bronchial hyperactivity, mucus production and airway inflammation. In this review, we discuss results from the literature that illustrate the potential of quercetin to treat asthma and its exacerbations.
Uniterms: Quercetin. Flavonoids. Asthma.A asma alérgica é uma doença inflamatória complexa caracterizada por hiperresponsividade das vias aéreas, inflamação eosinofílica e hipersecreção de muco. As terapias atuais incluem β 2 -agonistas, antagonistas do receptor 1 de cisteinil leucotrienos e corticosteróides. Embora estes fármacos demonstrem efeitos benéficos, seus efeitos adversos limitam seus usos a longo prazo. Assim, o desenvolvimento de novos compostos com atividades terapêuticas similares e reduzido efeitos adversos é tanto desejável quanto necessário. Compostos naturais podem ser utilizados nas terapias atuais, uma vez que metabólitos derivados de plantas são capazes de aliviar os sintomas de forma comparável aos medicamentos alopáticos. A quercetina é um flavonóide que ocorre naturalmente em muitas frutas e vegetais e tem mostrado vários efeitos biológicos, principalmente em modelos experimentais, incluindo a redução dos principais fenótipos da asma: hiperreatividade brônquica, produção de muco e inflamação das vias aéreas. Nesta revisão, nós discutimos os resultados da literatura que revelam o potencial da quercetina para tratar a asma e suas exacerbações.
“…26,27) Blocking of these proinflammatory cytokines might provide new therapeutic approaches for the control of allergic inflammation. 28) Cordycepin significantly inhibited the lipopolysaccharide (LPS)-induced release of TNF-α and IL-1β via the suppression of mitogen-activated protein kinases and NF-κB signaling pathways in RAW264.7 cells.…”
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.