Cytokines and Chemokines as Biomarkers of Future Asthma

Abstract

Antenatal and preschool factors are key in determining the progression to pre-school wheeze and eosinophilic school age asthma. The conventional view of eosinophilic asthma is that airway inflammation is the fundamental underlying abnormality, and airway inflammation and hyper-responsiveness are secondary; in fact, these three are parallel processes. Very early structural changes, independent of inflammation and infection, are associated with early airway hyper-responsiveness and later adverse respiratory outcomes. There is a bidirectional relationship between structural airway wall changes and airway inflammation, with airway contraction per se leading to the release of growth factors, and inflammatory pathways promoting airway remodeling. Early viral infection (and increasingly being appreciated, bacterial infection) is important in wheeze outcomes. There is evidence of abnormal immune function including cytokine release before the onset of viral infections. However, viral infections may also have prolonged effects on the host immune system, and the evidence for beneficial and adverse effects of viral infection is conflicting. In older children and adults, asthmatic epithelial cells show impaired interferon responses to viral infection, but only in the presence of uncontrolled type 2 inflammation, implying these are secondary phenomena. There are also compelling data relating the innate immune system to later asthma and atopy, and animal studies suggest that the effects of a high endotoxin, microbiologically diverse environment may be modulated via the epithelial alarmin IL-33. Whereas, previously only viral infection was thought to be important, early bacterial colonization of the upper airway is coming to the fore, associated with a mixed pattern of TH1/TH2/TH17 cytokine secretion, and adverse long term outcomes. Bacterial colonization is probably a marker of a subtle immune deficiency, rather than directly causal. The airway and gut microbiome critically impacts the development of Type 2 inflammatory responses. However, Type 2 inflammatory cytokines, which are critical both to progression from pre-school wheeze to eosinophilic asthma, and sustaining the eosinophilic asthmatic state, are not implicated in the very early development of the disease. Taken together, the evidence is that the earliest cytokine and chemokine signals will come from the study of bronchial epithelial cell function and their interactions with viruses and the microbiome.

Suppressive effects of S100A8 and S100A9 on neutrophil apoptosis by cytokine release of human bronchial epithelial cells in asthma

“…Airway epithelial cells play important roles in pathogenesis of asthma as structural cells. The relationship of airway epithelial cells and asthma differs, depending on the allergen, virus infection and effective mechanisms [13][14][15].…”

Relationship of inflammatory endothelial markers with the severity of asthma in children

“…The revealed correlations between endothelial markers of inflammation and the main parameters reflecting the functional state of the respiratory tract allows us to confirm that the chemoattractant MCP-1 plays a direct role in inflammation of the airways, promotes the growth of hypersensitivity and bronchial hyperactivity (27). The remaining elevated levels of endothelial markers of inflammation after the therapy create conditions for the development of chronic inflammation which stipulates progressive tracheobronchial tree remodeling (3,28,29). Ultimately irreversible changes in the bronchial ways lead to a decrease in FVC, VC.…”

Sesamol Alleviates Airway Hyperresponsiveness and Oxidative Stress in Asthmatic Mice

“…In the lungs of patients with asthma, Th2 cells secrete excess IL-4, IL-5, and IL-13 to inhibit the expression of Th1 cells, which reduces IFN-γ secretion [4]. Th2 cells secrete excess IL-4 to induce B cell activation and the secretion of more IgE antibodies [26]. When allergens combine with IgE and mast cells, the complex induces mast cells to release an excess of histamine and leukotriene, which causes a severe allergic reaction [27].…”

“…Next, mice inhaled 2% OVA administered with an ultrasonic nebulizer for 30 min to induce asthma symptoms (DeVilbiss Pulmo-Aide 5650D, United States) on days 14, 17, 20, 23, and 27. Then, for 2 weeks (days [14][15][16][17][18][19][20][21][22][23][24][25][26][27], in addition to their regular diet, each mouse group received a daily dose of saline (N and OVA groups), sesamol (S10 and S30 groups), or prednisolone (P group). On day 28, we calculated the AHR in all mice; then, on day 29, we sacrificed mice to investigate the asthma pathology, immune regulation, inflammation, and oxidative stress.…”