Notably, jejunum eosinophilia in IL-5-deficient-Fabpi-IL-18 mice is significantly induced compared with wild-type mice, which indicates the direct role of induced IL-18 in the tissue accumulation of eosinophils and mast cells.
Combined IL-2 Immunocomplex and Anti-IL-5 mAb Treatment Expands Foxp3<sup>+</sup> Treg Cells in the Absence of Eosinophilia and Ameliorates Experimental Colitis.
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.
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.
After epithelial barrier disruption, intranasal OVA application induced higher OVA-specific IgG1 and total IgE in serum, and increased eosinophilia and interleukin-5 in bronchoalveolar lavage (BAL) compared to sham-OVA mice.
In addition to evidence of mast cell activation, mucosa from patients with EoE have increased levels of interleukin 5; supporting eosinophilia; and upregulation of gene expression of eotaxin-3, a chemokine important in eosinophil migration.
In addition, eosinophils increased in the bronchoalveolar lavage fluids, alone with the elevated levels of Th-2 type cytokines [interleukin (IL)-4, IL-5 and IL-13], eotaxin, and adhesion molecules.
Strong granzyme B<sup>+</sup>, interferon (IFN)-γ<sup>+</sup> CD8<sup>+</sup> cytotoxic T cell and circulating regulatory T (T<sub>reg</sub>) cell responses were noted during allograft rejection, along with significant eosinophilia and elevated serum IL-5 and eotaxin levels.
In both models, targeted deletion of RORα in mouse T<sub>regs</sub> led to exaggerated eosinophilia driven by interleukin-5 (IL-5) production by ILC2s and T<sub>H</sub>2 cells.
Upstream Regulator Analysis revealed that not only T-helper 2 (Th2) and the eosinophilia-related molecules (interleukin 4 [IL4], IL5, and colony stimulating factor 2 [CSF2]) reported so far, but also cell cycle regulators (cyclin dependent kinase inhibitor 1A [CDKNA1] and cyclin D1 [CCND1]) and a tissue fibrosis-related molecule (transforming growth factor β [TGFβ]) were identified in ECRSwNP.
The most important cytokine involved in the induction, maintenance, and amplification of airway eosinophilia in asthma is interleukin-5 (IL-5), released by both T helper 2 (Th2) lymphocytes and group 2 innate lymphoid cells (ILC2).
These data are consistent with the hypothesis that the eosinophilia in FE is secondary to dysregulation of IL-5 production in PBMC (and their component subsets).
We investigated whether benralizumab, a monoclonal antibody directed against the alpha subunit of the interleukin-5 receptor that significantly reduces the incidence of asthma exacerbations, was also effective as an oral glucocorticoid-sparing therapy in patients relying on oral glucocorticoids to manage severe asthma associated with eosinophilia.
Based on the data presented, I propose omalizumab for patients with an allergic phenotype regardless of their peripheral eosinophilic count, and anti-IL-5 as an alternative in allergic patients with blood eosinophilia in which omalizumab has failed; anti-IL5 for patients with an eosinophilic phenotype and omalizumab as an alternative in patients in whom anti-IL5 fails and IgE ≥30 IU/mL (compassionate use).
Such a mechanism may explain the protective effect of parasite infection in patients with multiple sclerosis where eosinophilia is induced by IL-5, produced by the immune response to parasites.
Eosinophilic bronchitis is usually a Type 2 (T2)-driven process and therefore a sputum eosinophilia of greater than 3% usually indicates a response to treatment with corticosteroids or novel therapies directed against T2 cytokines such as IL-4, IL-5, and IL-13.
IL-5 neutralization before allergen challenge abolished the allergen-induced rise in circulating eosinophils and expression of IL-3 receptors, whereas airway eosinophilia and eosinophil peroxidase deposition were blunted but not eliminated.