Interleukin-4 and interferon gamma in bronchial remodeling in asthma patients with cold airway hyperresponsiveness

Interleukin-4 (IL-4) and interferon gamma (IFNγ) are key participants in the polarization of the immune response toward Th1 or Th2 types in bronchial asthma. However, their role in bronchial remodeling in patients with asthma and cold airway hyperresponsiveness (CAHR) remains unclear.
Aim. To study the involvement of IL-4 and IFNγ in the disorganization of bronchial epithelium and the regulation of airway remodeling in asthma with CAHR.
Materials and methods. A total of 47 patients with mild persistent asthma were examined. Induced sputum collection, blood sampling for biochemical studies, spirometry, and the isocapnic hyperventilation test with cold (-20 °C) air (IHCA) were performed. The sputum was analyzed for cellular composition (in %), and the cytokine profile (IL-4 and IFNγ in pg / ml) was evaluated in peripheral blood.
Results. The patients were divided into groups with CAHR (group 1, 17 patients) and without cold-induced bronchoconstriction (group 2, 30 patients). Forced expiratory volume in 1 sec. (FEV₁ ) and maximal mid-expiratory flow (MMEF) in group 1 were lower compared to group 2: 84.0[83.0; 93.0]% and 99.0 [85.0; 105.0]% (p = 0.012); 55.0[51.0;67.0]% and 76.0[59.0;88.0]% (p = 0.021), respectively. The blood content of IL-4 and IFNγ in group 1 was 11.48[10.82;22.48] pg / ml and 26.98[17.24; 73.5] pg / ml, while in group 2, it was 1.88 [0.66; 5.96] (p = 0.003) and 7.24[1.5; 26.98] pg / ml (p = 0.047), respectively. In group 1, an association was found between blood IL-4 and IFNγ levels (Rs = 0.65; p = 0.016), between FEV₁  and the number of epithelial cells in sputum (Rs = –0.74; p = 0.0003), and between IL-4 and airway response (ΔFEV₁ /Vital Capacity) after the IHCA (Rs = –0.70; p = 0.007).
Conclusion. The escalation of the proinflammatory and pro-oxidant function of IFNγ indicates a shift from Th2 immune response activation, regulated by IL-4, toward a Th1 response, which stimulates bronchial remodeling in patients with asthma and CAHR.

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