Journal of Allergy and Clinical Immunology
Novel Therapies in Allergic DiseaseCytokine-directed therapies for asthma☆,☆☆
Section snippets
Strategic approaches
Several strategies for inhibiting proinflammatory cytokines have been considered. At the most basic level, cytokine synthesis can be inhibited by blocking the transcription factors that lead to the expression of those cytokines. In this context, the potential of nuclear factor-κB as a target has received considerable attention because it regulates the expression of multiple cytokines involved in asthma. Alternatively, an antisense oligonucleotide can be used to “mop up” the messenger RNA, thus
Interleukin-5
IL-5 plays a key role in the airway inflammation of asthma. It is essential for the production, maturation, activation, and survival of eosinophils and is also important in eosinophil chemoattraction.3 The central role of IL-5 among cytokines in the development of eosinophilia has been demonstrated in many in vivo models. Pretreatment with anti–IL-5 monoclonal antibodies has been shown to suppress allergen-induced airway eosinophilia in guinea pigs and monkeys.4, 5 In a cynomolgus monkey model
Interleukin-10
IL-10 has unique functional effects, a number of which are relevant to asthma. It inhibits the production of several proinflammatory cytokines such as IL-1β, TNF-α, and GM-CSF, as well as chemokines, particularly eotaxin and RANTES, that could be important for eosinophil recruitment.17 It also inhibits the inflammatory enzymes, such as insoluble nitric oxide synthase (iNOS) and insoluble cyclooxygenase (COX-2), potently blocks IL-5, inhibits TH2 cytokines, and reduces allergen responses by
Conclusions
Anti–IL-5 antibodies are highly effective in the long-term reduction of eosinophils. The fact that no effect on airway reactivity has been observed with anti–IL-5 treatment is disappointing, but this approach nonetheless merits further study in patients with symptomatic asthma. Evidence that IL-4 receptor antagonists have some clinical benefit in asthma when administered by inhalation is encouraging and also merits further investigation, especially since administration as a single weekly dose
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Cited by (72)
Propofol inhibits NF-κB activation to ameliorate airway inflammation in ovalbumin (OVA)-induced allergic asthma mice
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2016, International ImmunopharmacologyCitation Excerpt :IL-13 has the ability to induce airway inflammation and AHR [21]. Recent studies suggested that inhibition of these Th2 cytokines might be a potential therapeutic strategy for the treatment of allergic asthma [22]. In this study, we found that treatment of AA significantly inhibited OVA-induced IL-4, IL-5, and IL-13 production in a dose-dependent manner.
The IL6R gene polymorphisms are associated with sIL-6R, IgE and lung function in Chinese patients with asthma
2016, GeneCitation Excerpt :IgE is a mediator of airway inflammation response and is considered an important biomarker for asthma (Bachert & Zhang, 2012; Beeh et al., 2000). IL-4 promotes the production of IgE (Berton et al., 1989), and had been considered to be a target for blocking IgE production in allergic asthma(Barnes, 2001). IL-6 promotes endogenous IL-4 production in CD4 T cells (Diehl et al., 2002; Neveu et al., 2009).
Targeted therapies in severe asthma: The discovery of new molecules
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2012, Clinics in Chest MedicineCitation Excerpt :Accordingly, blocking one cytokine will be sufficient to avoid the risk of redundancy and potentially a subsequent clinical failure.42,43 IL-4 and IL-13 are thought to play distinct important roles in B-cell commutation to IgE production, mast cell expression of the IgE receptor (fragment crystallizable [Fc] epsilon R [FcεRI]), and eosinophil recruitment.44–46 Clinical trials using monoclonal antibodies (mAbs) directed toward IL-4 and IL-4R failed to demonstrate a clinical impact on asthma outcomes.47–49
Amphetamine modulates cellular recruitment and airway reactivity in a rat model of allergic lung inflammation
2011, Toxicology LettersCitation Excerpt :It is important to note that amphetamine treatment reduced the Mac-1 expression in both macrophages and granulocytes. Cytokines, especially IL-4, IL-5, IL-10, and IL-13, are expressed during asthma (Barnes, 2001). Cytokines and their activation of adhesion molecules can then contribute to cell infiltration and activation during allergic lung inflammation, which might explain the elevated levels of IL-10 and IL-4 found in samples of lung explants from allergic rats.
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Dr Barnes has consultant arrangements with GlaxoSmithKline and receives research support from GlaxoSmithKline, Boehringer Ingelheim, Novartis, and Bayer. He is also an employee of Imperial College, London.
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Reprint requests: Peter J. Barnes, MD, DM, DSc, National Heart and Lung Institute, Division of Thoracic Medicine, Dovehouse Street, London, SW3 6LY, UK.