Abstract
Background: It has been shown that certain severe and refractory asthma cases are due to neutrophil and not eosinophil infiltration. ICOSL (Inducible costimulatory molecular ligand) expression is closely associated with tumor and autoimmune diseases, while a limited amount of data has been published regarding the significance of ICOSL in children with neutrophilic asthma. The present study aimed to explore the abnormal expression of ICOSL in peripheral blood and bronchoalveolar lavage fluid (BALF) samples of children with neutrophilic asthma and their clinical significance. Methods: The present clinical study selected children who met the diagnostic criteria of asthma from the children's Hospital of Suchow University and excluded the patients with positive etiology. The children who were admitted to the hospital for foreign body inhalation in the same period were collected as the control group. The children with more than 50% (the percentage of neutrophils in BALF was 95% of the percentile in the control group) of neutrophils in BALF samples were assigned to the neutrophilic asthma group (NA group), whereas the remaining subjects comprised the asthma group (A group). The expression levels of ICOSL, IL-4, IL-17, IFN-, neutrophil elastase (NE) and matrix metalloproteinase (MMP)-9 were detected in plasma and BALF samples by enzyme-linked immunosorbent assays in order to analyze the differences in the levels of cytokines and clinical characteristics between children with neutrophilic asthma and non-neutrophilic asthma. Moreover, the potential mechanism of ICOSL in neutrophilic asthma was explored. Results: In strict accordance with the diagnostic criteria of asthma and following exclusion of pathogenic positive children, 32 children were finally enrolled, including 12 children in the NA group and 20 children in the A group. The mean hospitalization time of the NA group was longer than that of the A group (P<0.05). The concentration levels of ICOSL, IL-17, NE and MMP9 of the NA group in plasma and BALF samples were higher than those in the A group, while the levels of IFN-γ exhibited the opposite trend. A significant correlation was evident between ICOSL and IL-17 levels in plasma(r=0.753,P=0.012) and BALF(r=0.774,P=0.009)samples of the NA group. Conclusion: Children with asthma exhibited an immunity imbalance of Th1/Th2/Th17, whereas neutrophilic asthma children were more severely affected. The clinical treatment was considerably difficult and the hospitalization time was longer. ICOSL may regulate the secretion of IL-17 by Th17 and increase the levels of NE and MMP9, which are involved in the development of immune inflammation in neutrophils.