From: Treatment of allergic asthma: Modulation of Th2 cells and their responses
Cytokine | Relation to Th2 cells in asthma | References | Was the target used in clinical trials in asthma? | Clinical study, Reference* |
---|---|---|---|---|
IL-2 | Important for survival of mature Tregs Required for generation of effector and survival of memory T cells | [175] [222] | Yes, daclizumab targeting its soluble IL-2 receptor CD25, improves FEV1 and reduced daily asthma symptoms | |
IL-3 | Secreted by Th2 cells, regulates eosinophil and basophil differentiation, migration and survival Inhibition of IL-3/IL-5/GM-CSF common β receptor inhibits Th2 differentiation | [225] | No | - |
IL-4 | Crucial for Th2 cell differentiation Induction of IgE production of B cells | [226] | Yes, numerous mAbs and other compounds, development of most mAbs was discontinued, pitrakinra (IL-4 mutant protein binding to IL-4 and IL-13 receptors) improves lung function, stabilises asthma symptom scores and reduces beta-agonist use | [9, 11, 227–229], NCT00801853, NCT00941577 |
IL-5 | Th2 cell cytokine involved in eosinophil differentiation, maturation, recruitment and survival | Yes, does not inhibit eosinophilia or AHR, but new indications suggest use in difficult-to-treat and severe asthma | [232–234], NCT01000506, NCT00292877 | |
IL-6 | Polarises CD4+ T cells to Th2 or Th17 subtype Soluble IL-6 receptor induces apoptosis of Th2 cells in the lungs & induces Tregs | [237] | No | - |
IL-9 | Secreted by Th2 cells Over expression in mice enhances inflammation and AHR | [238] | Yes, appears to have acceptable safety profile and to decrease FEV1 | |
IL-10 | Secreted by Th2 cells and some Tregs, plays multiple roles in the immune processes | [243] | No | - |
IL-12 | Essential for differentiation, proliferation and activation of Th1 cells Suppresses Th2 immune responses in murine models | [244] [245] | Yes, reduction in the number of circulating blood eosinophils, but not sputum eosinophilia, the late-phase response or airway hyper-responsiveness | [246] |
IL-13 | Involved in lung inflammation, mucus hypersectretion, subepithelial fibrosis and eotaxin production | [247] | Yes, clinical trials for numerous mAbs are in progress; pitrakinra (IL-4 mutant protein binding to IL-4 and IL-13 receptors) improves lung function, stabilises asthma symptom scores and reduces beta-agonist use | |
IL-15 | Th1 cytokine that appears to counterbalance Th2 immune response | [250] | No | - |
IL-17A | Implicated in infiltration of neutrophils after allergen exposure Might regulate established Th2 response | [251] [252] | No | - |
IL-17F | Implicated in infiltration of neutrophils after allergen exposure | [251] | No | - |
IL-18 | Cytokine involved in Th1 and Th2 immunity Delivery of IL-18 gene reduced allergic inflammation in a mouse asthma model | [253] [254] | No | - |
IL-19 | Produced by epithelial cells and mediates IL-4, IL-5, IL-10 and IL-13 production | No | - | |
IL-21 | Secreted by CD4+ T cells Involved in proliferation, differentiation and regulation of T cells, B cells, DCs and natural killer cells Stimulates IgG responses instead of IgE | No | - | |
IL-22 | Required for the onset of allergic asthma in mice, but negatively regulates acute inflammation in lungs | [258] | No | - |
IL-23 | Lung-specific expression enhances allergen-induced inflammation, mucus hyperproduction and AHR Its inhibition protects against allergic asthma in mice | [259] [260] | No | - |
IL-25 | Induces Th2 immunity, enhances Th2 cell survival and stimulates Th2 cytokine secretion Its inhibition prevents inflammation in mouse models of asthma | No | - | |
IL-27 | Th1 cytokine decreases Th2 response in murine models of asthma | [263] | No | - |
IL-31 | Secreted by Th2 cells, expressed at higher levels in asthmatic patients | No | - | |
IL-33 | IL-33 receptor, ST2, is a marker for Th2 cells IL-33 activates Th2 cells | [268] | No | - |
IFN-γ | Th1 cytokine that inhibits Th2 cell polarisation in vitro Appears to be involved in pathogenesis of severe allergic asthma | [40] | Yes, but treatment did not improve monitored clinical parameters | [271] |
TGF-ß | TGF-ß inhibits expression of transcription factor GATA-3 Its neutralisation exacerbates or has no effect on inflammatory responses in mouse models of asthma | [272] | No | - |
TNF-α | Pleiotropic cytokine, chemoattractant for eosinophils and contributes to the activation of T cells | [275] | Yes, divergent results, severe side-effects |