The authors analyze the possible implication of 7 genetic polymorphisms described as asthma susceptibility genes: IL13 (C-1112T and R130Q), IL4RA (I50V, Q551R), IL5 (C-746T) and ADRB2 (Q27E and R16G) in specific olive pollen allergic sensitization.
We conducted an association study between known polymorphisms of IL-5 (T-746C) and TBXA2R (T924C) and asthma phenotype and the parameters of atopy and pulmonary function in atopic and nonatopic Korean children with asthma.
Concanavalin A (ConA)-stimulated blastocytes derived from peripheral blood lymphocytes of asthmatic subjects were transiently transfected with the human IL-5 gene promoter/enhancer-luciferase gene construct, pIL-5 (-511)Luc, and cultured with THP-1 cells (human monocytoid cells) and anti-CD3 monoclonal antibody (mAb).
Pathogenic T helper 2 (T<sub>H</sub>2) cells, which produce increased amounts of the cytokines interleukin-5 (IL-5) and IL-13, promote allergic disorders, including asthma.
In comparison with that in the healthy control (HC), significantly lower abundance of Bifidobacterium and lower levels of Th1 cytokines (IFN-γ and TNF-α), but higher levels of Th2-type cytokines (IL-4, IL-5) and Th17-type (IL-17A) cytokine were detected in children with bronchiolitis and asthma.
In contrast, spleens of sensitized and challenged Tg mice contained increased numbers of CD4(+)CCR3(+) cells producing more Th2-type cytokines (IL-4, IL-5, and IL-13), which were associated with increased airway hyperreactivity.
In two large study populations of children, the German part of the International Study of Asthma and Allergy in Childhood (ISAAC II) and the German Multicentre Atopy Study (MAS), 3099 and 824 children, seven polymorphisms previously associated with the development of atopic diseases were genotyped: two in and around the GM-CSF gene (Ile117Thr and T3085G), one in IL-3 (Pro27Ser), in IL-5 (C-746T), and in the IL-5 high affinity receptor chain IL-5R (G-80A) and two in the common receptor chain CSFR2b for IL-3, IL-5, and GM-CSF (Asp312Asn and Glu249Gln).
In sharp contrast, B7-H3 KO mice developed severe ovalbumin (OVA)-induced asthma with characteristic infiltrations of eosinophils in the lung, increased IL-5 and IL-13 in lavage fluid, and elevated IgE anti-OVA antibodies in the blood.
<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).
Monoclonal antibodies targeting IL-5 or its receptor (IL-5R) have been developed, with recent studies suggesting that they reduce asthma exacerbations, improve health-related quality of life (HRQoL) and lung function.
All these IL-5 target drugs have been shown to reduce the number of exacerbation in patients with severe asthma selected on the basis of peripheral blood eosinophil count.
These observations suggest that IL-5 synthesis by activated T-lymphocytes may be relevant to the pathogenesis of asthma, and that inhibition of this release by glucocorticoids may at least partly explain their therapeutic effect in this disease.
We tested for possible associations between SNPs in the IL33 and ST2 with asthma and allergy markers such as specific IgE (sIgE), IL-5 and IL-13 production and skin prick test (SPT).