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
相关论文
共 28 条
[21]   The human glucocorticoid receptor beta isoform - Expression, biochemical properties, and putative function [J].
Oakley, RH ;
Sar, M ;
Cidlowski, JA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (16) :9550-9559
[22]   Oral Prednisolone for Preschool Children with Acute Virus-Induced Wheezing. [J].
Panickar, Jayachandran ;
Lakhanpaul, Monica ;
Lambert, Paul C. ;
Kenia, Priti ;
Stephenson, Terence ;
Smyth, Alan ;
Grigg, Jonathan .
NEW ENGLAND JOURNAL OF MEDICINE, 2009, 360 (04) :329-338
[23]  
Patel H., 2004, Cochrane Database Syst. Rev, V3, pCD004878, DOI [10.1002/14651858.CD004878, DOI 10.1002/14651858.CD004878]
[24]   T helper 1/T helper 2 cytokine imbalance in respiratory syncytial virus infection is associated with increased endogenous plasma cortisol [J].
Pinto, RA ;
Arredondo, SM ;
Bono, MR ;
Gaggero, AA ;
Díaz, PV .
PEDIATRICS, 2006, 117 (05) :E878-E886
[25]   Respiratory syncytial virus infection in infants is associated with predominant Th-2-like response [J].
Roman, M ;
Calhoun, WJ ;
Hinton, KL ;
Avendano, LF ;
Simon, V ;
Escobar, AM ;
Gaggero, A ;
Diaz, PV .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 1997, 156 (01) :190-195
[26]   Genomewide Association between GLCCI1 and Response to Glucocorticoid Therapy in Asthma [J].
Tantisira, Kelan G. ;
Lasky-Su, Jessica ;
Harada, Michishige ;
Murphy, Amy ;
Litonjua, Augusto A. ;
Himes, Blanca E. ;
Lange, Christoph ;
Lazarus, Ross ;
Sylvia, Jody ;
Klanderman, Barbara ;
Duan, Qing Ling ;
Qiu, Weiliang ;
Hirota, Tomomitsu ;
Martinez, Fernando D. ;
Mauger, David ;
Sorkness, Christine ;
Szefler, Stanley ;
Lazarus, Stephen C. ;
Lemanske, Robert F., Jr. ;
Peters, Stephen P. ;
Lima, John J. ;
Nakamura, Yusuke ;
Tamari, Mayumi ;
Weiss, Scott T. .
NEW ENGLAND JOURNAL OF MEDICINE, 2011, 365 (13) :1173-1183
[27]   Regulation of the hypothalamic-pituitary-adrenal axis by cytokines: Actions and mechanisms of action [J].
Turnbull, AV ;
Rivier, CL .
PHYSIOLOGICAL REVIEWS, 1999, 79 (01) :1-71
[28]   Proinflammatory cytokines regulate human glucocorticoid receptor gene expression and lead to the accumulation of the dominant negative β isoform:: A mechanism for the generation of glucocorticoid resistance [J].
Webster, JC ;
Oakley, RH ;
Jewell, CM ;
Cidlowski, JA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (12) :6865-6870