The Changes of Th17/Treg and Related Cytokines: IL-17, IL-23, IL-10, and TGF-ß in Respiratory Syncytial Virus Bronchiolitis Rat Model.

Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and hospitalization that lead to high morbidity and mortality among young infants. T helper 17 (Th17) cells and regulatory T cells (Tregs) play essential roles in the pathogenesis of autoimmune, cancer, and inflammatory diseases. However, whether changes in T-cell subsets are related to the systemic immune responses in RSV-caused bronchiolitis merit further investigation. Three-week-old Sprague Dawley (SD) rats were randomly divided into the normal control (NC) and RSV bronchiolitis (RSV-B) groups. An RSV-B model was successfully established using nasal drip containing RSV. Furthermore, pathological changes in the lung tissues were observed using hematoxylin and eosin staining. Flow cytometry determined the levels of Th17 and Treg subsets. The related cytokines were measured using enzyme-linked immunosorbent assay (ELISA). The expression levels of related transcription factors, such as RORγt and FOXP3, were examined using real-time quantitative PCR and western blot analysis. The RSV-B group exhibited pulmonary interstitial hyperemia and edema, inflammatory cell infiltration, wide alveolar septa, and bronchial collapse and deformation. The percentage of Th17 cells in RSV-B group was about 2.3 fold higher than that of NC group, and the concentration of IL-17, IL-23 and RORγt was higher than in NC group. In contrast, the percentage of Treg cells in the RSV-B group was approximately 0.7 fold lower than that in the NC group, and the levels of IL-10, TGF-ß, and FOXP3 in the RSV-B group were lower than those in the NC group. The above results were statistically significant. The changes of Th17/Treg, and their associated cytokines, specific transcription factors, are present in RSV bronchiolitis model rats, which may play an important role in the pathogenesis of RSV bronchiolitis.

[Changes and the clinical significance of CD4⁺ CD25⁺ regulatory T cells and Th17 cells in peripheral blood of infants with respiratory syncytial virus bronchiolitis].

AIM: To observe the percentages of CD4(+);CD25(+); regulatory T cells (Tregs) and Th17 cells and the levels of IL-10, TGF-ß and IL-17 in peripheral blood of infants with respiratory syncytial virus (RSV) bronchiolitis. The relationship between above cells, cytokines and RSV bronchiolitis was determined. METHODS: Thirty-three infants with RSV bronchiolitis, twenty-eight infants with non-RSV pneumonia and twenty-six healthy infants were enrolled. The percentages of Tregs and Th17 cells in peripheral blood were detected by flow cytometer (FCM), and the levels of IL-10, TGF-ß and IL-17 in plasma were determined by ELISA. RESULTS: The percentage of Tregs and the levels of IL-10 and TGF-ß in infants with RSV bronchiolitis were significantly lower than those in infants with non-RSV pneumonia and healthy infants (P<0.05), while the percentage of Th17 cells and the level of IL-17 in infants with RSV bronchiolitis were significantly higher than those in infants with non-RSV pneumonia and healthy infants (P<0.05). CONCLUSION: The imbalance between Tregs and Th17 cells in peripheral blood of infants with RSV bronchiolitis may be one of the pathogenesis of RSV bronchiolitis.

[Relationship between variation of coxsackievirus B3 VP1 sequence from cerebrospinal fluid of children and severity of damage to central nervous system].

OBJECTIVE: To investigate the possible relationship between variation of coxsackievirus B3 (CoxB3) VP1 sequence from cerebrospinal fluid of children with severe and mild central nervous system (CNS) infection and damage to CNS in children from Shandong province. METHODS: The enteroviruses were detected using VP1 typing and sequencing primer for enteroviruses from 73 enterovirus-infected cases confirmed by detection of cerebrospinal fluid by enteroviruses common primer. VP1 sequences (450 nucleotides) were determined and analyzed for 21 CoxB3 enteroviruses strains isolated in Qingdao and Binzhou, and were compared with that of BLAST search procedures from GeneBank in NCBI. The variation of VP1 gene and amino acids sequence of CoxB3 enteroviruses was analyzed for severe and mild CNS infection. RESULTS: The nucleotide homogeneity of these CoxB3 appeared to be 97% - 99%, however, the homogeneity among different genotypes were 83% - 76%. Replacement of glutamine by histidine at amino acid locus 856 of VP1 CoxB3 was found in 4 cases with severe encephalitis. There were different variation in VP1 nucleotide sequence of CoxB3 in 3 cases with mild encephalitis and 14 cases with meningitis, but amino acids sequences had no regular variation. The modified Glasgow's coma score was below 7 in all the 4 cases with severe encephalitis. Of these 4 cases, 3 had consciousness disturbance for less than 3 days. Lethargy, restlessness and psychiatric symptoms were major manifestations, of whom 3 also had dysphagia, 1 had encephalatrophy obviously, Glasgow's coma score was 3, deep coma lasted for 9 days, and had concomitant fatal epileptic attacks. Of these 4 cases, 2 completely recovered, 1 had high muscle tone, 1 remained under anti-epileptic drug treatment at follow-up 6 months later. CONCLUSION: There were a small epidemic of CoxB3 CNS infection in children in 2005 in this area. The amino acid variation of CoxB3 VP1 possibly caused increased viral virulence and caused damage to CNS.