Increased Expression of the Glucocorticoid Receptor β in Infants With RSV Bronchiolitis

被引:23
作者
Diaz, Patricia V. [1 ]
Pinto, Ricardo A. [4 ]
Mamani, Rossana [4 ]
Uasapud, Paola A. [6 ]
Bono, Maria R. [5 ]
Gaggero, Aldo A. [2 ]
Guerrero, Julia [3 ]
Goecke, Annelise [3 ]
机构
[1] Univ Chile, Fac Med, Pathophysiol Program, Inst Ciencias Biomed, Santiago 7, Chile
[2] Univ Chile, Fac Med, Virol Program, Inst Ciencias Biomed, Santiago 7, Chile
[3] Univ Chile, Fac Med, Physiol Program, Inst Ciencias Biomed, Santiago 7, Chile
[4] Univ Chile, Fac Med, Dept Pediat, Santiago 7, Chile
[5] Univ Chile, Fac Sci, Dept Biol, Santiago, Chile
[6] Ctr Salud Familiar Agustin Cruz Melo, Serv Salud Metropolitano N, Santiago, Chile
关键词
RSV bronchiolitis; infants; glucocorticoid receptor; interleukin-6; interleukin-8; RESPIRATORY SYNCYTIAL VIRUS; INSENSITIVE ASTHMA; GENE-EXPRESSION; KAPPA-B; CELLS; INFECTION; ASSOCIATION; ACTIVATION; MECHANISMS; IMBALANCE;
D O I
10.1542/peds.2012-0160
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
OBJECTIVES: The majority of studies on glucocorticoid treatment in respiratory syncytial virus (RSV) bronchiolitis concluded that there are no beneficial effects. We hypothesized that RSV-infected patients may have an increased glucocorticoid receptor (GR) beta expression, the isoform that is unable to bind cortisol and exert an antiinflammatory action. METHODS: By using real-time polymerase chain reaction, we studied the expression of alpha and beta GR in the peripheral blood mononuclear cells obtained from 49 RSV-infected infants (<1 year of age) with severe (n = 29) and mild to moderate (n = 20) illness. In plasma, we analyzed the level of cortisol by radioimmunoassay and inflammatory cytokines interleukin (IL)-10, IL-6, tumor necrosis factor-alpha, IL-1 beta, IL-8, IL-12p70, IL-2, IL-4, IL-5, interferon-gamma, and IL-17 by cytometric beads assay. Statistical analysis was performed by nonparametric analysis of variance. RESULTS: We found a significant increase of beta GR expression in patients with severe illness compared with those with mild disease (P < .001) and with a group of healthy controls (P < .01). The alpha:beta GR ratio decreased significantly in infants with severe disease compared with those with mild illness (P < .01) and with normal controls (P < .001). The expression of beta GR was positively correlated with the clinical score of severity (r = .54; P < .0001). CONCLUSIONS: The decrease of the alpha:beta GR ratio by an increase of beta receptors expression is related to illness severity and may partly explain the insensitivity to corticoid treatment in RSV-infected infants. The increased expression of beta GR could be a marker of disease severity. Pediatrics 2012; 130: e804-e811
引用
收藏
页码:E804 / E811
页数:8
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