This article reviews the role of eosinophils in the pathogenesis of bronchial asthma and discusses the potential advantageous biologic effects of benralizumab in comparison with other monoclonal antibodies targeting the IL-5 ligand.
We show that transgenic mice that overexpress interleukin-5 (IL-5), a cytokine required for eosinophil hematopoiesis, give birth to WT offspring that have significantly increased airway epithelial nerve density and airway hyperreactivity that persists into adulthood.
<b>Expert opinion</b>: IL-5 antagonism has paved the way for an additional personalized therapeutic opportunity for use in severe asthma with eosinophilic inflammation, though there is limited evidence on the long-term implications of suppressing/depleting eosinophils and the duration for which they should be administered.
Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of immunoglobulin E (IgE), interleukin-5 (IL-5), nerve growth factor (NGF) and interferon-γ (IFN-γ) in asthma allergy.
The mechanism of MSC therapy in asthma seems to be regulating the balance of Th1 cytokine and Th2 cytokines (IFN-γ: Hedges's g = 4.779 ± 1.408 with 95% CI: 1.099-2.725, P < 0.001; IL-4: Hedges's g = -10.781 ± 1.062 with 95% CI: -12.863 ∼ -8.699, P < 0.001; IL-5: Hedges's g = -10.537 ± 1.269 with 95% CI: -13.025 ∼ -8.050, P < 0.001; IL-13: Hedges's g = -6.773 ± 0.788 with 95% CI: -8.318 ∼ -5.229, P < 0.001).
Preventive treatment with L. rhamnosus GG (but not L. rhamnosus GR-1) resulted in a significant decrease in bronchoalveolar lavage eosinophil counts, lung interleukin-13 and interleukin-5 levels, and airway hyperreactivity.
Type-2 biomarkers and related cytokines (IL-5, IL-13), lung function and asthma symptoms were measured in 44 poorly-controlled severe oral corticosteroid (OCS)-dependent asthmatics for up to 88 days after a 7-day prednisolone boost (0.5 mg/kg).
The role of eosinophilia in atopic diseases, including asthma, is well established, as is the well-known role of IL-5 as a major eosinophilopoeitin and chemoattractant.
Eosinophil differentiation, survival, and activation are preferentially regulated by IL-5, a cytokine that binds to the IL-5 receptor (IL-5R), which is located on the surface of eosinophils or basophils and plays a critical role in the pathogenesis and severity of asthma.
The IL-5 in sputum supernatant was significantly decreased in stable COPD patients with positive BD tests as compared with the patients with asthma (12.5±7.8 vs. 48.2±26.0 ng/mL;.P<0.01).
Eosinophilic COPD may represent an overlap with asthma but the mechanism of eosinophilia is uncertain as, although an increase in sputum IL-5 has been detected, anti-IL-5 therapies are not effective in preventing exacerbations.
In EGPA, although maintenance treatment with the interleukin-5 antagonist mepolizumab is effective in decreasing glucocorticoid requirements and in alleviating asthma and sinonasal symptoms, its efficacy on the vasculitis remains somewhat unclear.
ST2<sup>+</sup> memory CD4<sup>+</sup> T cells have the capacity to produce high levels of IL-5 and Amphiregulin and are involved in the pathology of asthma.
Although these pathognomonic features are mainly mediated by antigen-specific Th2 cells and their cytokines, such as IL-4, IL-5, and IL-13, recent studies have revealed that other inflammatory cells, including Th17 cells and innate lymphoid cells (ILCs), also play a critical role in the pathogenesis of asthma.
The administration of anti-IL-5 or anti-IL-5 receptor (IL-5R) antibodies has been shown to reduce eosinophil counts and ameliorate asthmatic symptoms in studies on animal models of allergy as well as in human clinical trials.
In addition to anti-IgE therapy that has improved outcomes in allergic asthma for more than a decade, three anti-IL-5 biologics and one anti-IL-4R biologic have recently emerged as promising treatments for T2 asthma.
We assessed the effect of placenta-derived MSCs on T cell immune responses and cytokine IL-5 levels according to cultures in children with and without asthma.
In an ovalbumin (OVA)-induced asthmatic model, inhaled MHF showed significant suppression of airway hyperresponsiveness; a decrease in eosinophil and neutrophil counts, IL-4, IL-5 and leukotriene D<sub>4</sub> in bronchoalveolar lavage fluid; a reduction in total IgE and OVA-specific IgE levels in serum; and suppression of eosinophil infiltration in lung tissue after antigen challenge.
In recent studies, patients with severe, uncontrolled asthma and high eosinophil counts respond to biologic therapies targeting the type-2 signaling pathway and eosinophils themselves (eg, anti-IL-5 therapy).
Mepolizumab (anti IL-5, monoclonal antibody) is commercially available in Italy since more than one year for the treatment of severe hypereosinophilic asthma.