Peripheral Blood MDSCs, IL-10 and IL-12 in Children with Asthma and Their Importance in Asthma Development

Abstract

ObjectiveTo investigate myeloid-derived suppressor cell (MDSC) accumulation and interleukin 10 (IL-10) and interleukin 12 (IL-12) levels during the onset of asthma in both pediatric patients and mouse models, as well as their possible roles in the development of asthma.MethodsPeripheral blood samples were gathered from children with asthma attacks (attack group) and alleviated asthma (alleviated group), as well as two control groups, children with pneumonia and healthy children. The pathological characteristics of asthma in asthmatic mice, budesonide-treated asthmatic mice, and normal control mice were also evaluated by immunohistochemistry (IHC) and hematoxylin and eosin (H&E) staining.ResultsMDSC accumulation and serum IL-10 levels were significantly elevated in the children with asthma compared with the budesonide-treated alleviated group, normal healthy controls, and pneumonia controls (p<0.05), whereas those in the latter three groups showed no statistical differences (p>0.05). The level of serum IL-12 in the asthmatic children was drastically reduced compared to the budesonide-treated alleviated group, healthy controls, and pneumonia controls (p<0.05), whereas the latter three groups showed no significant differences in their serum IL-12 levels. The percentage of MDSCs in children with asthma was positively correlated with the level of serum IL-10 and negatively correlated with the level of serum IL-12. The levels of MDSCs and IL-10 in asthmatic mice were significantly higher than those in the normal control mice (both p<0.05) and were reduced after budesonide treatment (both p<0.05). IL-12 expression in the asthmatic mice was significantly lower than the control and was increased upon budesonide treatment (both p<0.05).ConclusionDuring the onset of asthma, the accumulation of MDSCs and the level of serum IL-10 increase, while the level of IL-12 decreases. These fluctuations may play an important role in the development of asthma.

Defective IL-10 expression and in vitro steroid-induced IL-17A in paediatric severe therapy-resistant asthma

“…This is consistent with recent reports of IL-10 polymorphisms in paediatric asthma31 and with the defective IL-10 expression observed in adult asthma 17 18 20 32. In children with well-controlled asthma who are on steroids, serum IL-10 is similar to controls 33. However, we have seen that when we look in the airways, even those with moderate, well-controlled asthma have lower levels of IL-10 than controls, emphasising the importance, where feasible, of looking in BAL samples.…”

The emerging role of myeloid-derived suppressor cells in lung diseases

“…Several studies demonstrate that the immunosuppressive functions of MDSCs require cell-cell contact, suggesting that MDSCs act through cell-surface receptors and/or the release of short-lived paracrine mediators [7]. MDSCs produce the anti-inflammatory cytokine IL-10 and dampen both CD4 + T-cells and NK cell responses [7,75,76], while promoting the expansion of Treg [63] and M2-like macrophages [59].…”

“…IL-10 not only suppressed the production of pro-inflammatory factors by macrophages, but also reduced cytotoxic effects and decreased NO production. Therefore, it is proposed that MDSCs play a dual role in asthma by upregulating anti-inflammatory IL-10 and downregulating pro-inflammatory IL-12 [76]. In a different study, MDSCs enhanced mast cell-mediated secretion of several inflammatory cytokines, including TNF, IL-6, IL-13, macrophage inflammatory protein-1α and monocyte chemoattractant protein-1.…”

Immune biomarkers in the spectrum of childhood noncommunicable diseases

“…Similarly, inflammatory markers (IL-2, IL-4, IL-8 and IL-10) in exhaled breath condensate at 2 -3 years of age were elevated among children who were persistent wheezers up to 5 years of age compared to children who had never wheezed 99,100 . Further study is required to evaluate the efficacy of these as clinically useful biomarkers.…”