Decreased interleukin-12 levels in umbilical cord blood in children who developed acute bronchiolitis

Blanco‐Quirós, Alfredo; González, Hermenegildo; Arranz, Eduardo; Lapeña, Santiago

doi:10.1002/(sici)1099-0496(199909)28:3<175::aid-ppul3>3.0.co;2-u

Cited by 58 publications

(36 citation statements)

References 38 publications

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“…This may be especially interesting considering that peak viral titers from the lungs occur around day 4 of infection, whereas the pathophysiologic responses occur at a later time point. Altered immune response related to IL-13 regulation of IL-12 correlates with recent studies demonstrating a decrease in IL-12 in those children who developed RSV-induced bronchiolitis (41). In these studies, we found increases in IFN-␥ levels in lung homogenates at earlier time points that preceded peak airway hyperreactivity.…”

Section: Discussionsupporting

confidence: 87%

IL-13-Induced Airway Hyperreactivity During Respiratory Syncytial Virus Infection Is STAT6 Dependent

Tekkanat

Maassab

Cho

et al. 2001

The Journal of Immunology

129

109

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Airway damage and hyperreactivity induced during respiratory syncytial virus (RSV) infection can have a prolonged effect in infants and young children. These infections can alter the long-term function of the lung and may lead to severe asthma-like responses. In these studies, the role of IL-13 in inducing and maintaining a prolonged airway hyperreactivity response was examined using a mouse model of primary RSV infection. Using this model, there was evidence of significant airway epithelial cell damage and sloughing, along with mucus production. The airway hyperreactivity response was significantly increased by 8 days postinfection, peaked during days 10–12, and began to resolve by day 14. When the local production of Th1- and Th2-associated cytokines was examined, there was a significant increase, primarily in IL-13, as the viral response progressed. Treatment of RSV-infected mice with anti-IL-13 substantially inhibited airway hyperreactivity. Anti-IL-4 treatment had no effect on the RSV-induced responses. Interestingly, when IL-13 was neutralized, an early increase in IL-12 production was observed within the lungs, as was a significantly lower level of viral Ags, suggesting that IL-13 may be regulating an important antiviral pathway. The examination of RSV-induced airway hyperreactivity in STAT6−/− mice demonstrated a significant attenuation of the response, similar to the anti-IL-13 treatment. In addition, STAT6−/− mice had a significant alteration of mucus-producing cells in the airway. Altogether, these studies suggest that a primary factor leading to chronic RSV-induced airway dysfunction may be the inappropriate production of IL-13.

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Section: Discussionsupporting

confidence: 87%

IL-13-Induced Airway Hyperreactivity During Respiratory Syncytial Virus Infection Is STAT6 Dependent

Tekkanat

Maassab

Cho

et al. 2001

The Journal of Immunology

129

109

View full text Add to dashboard Cite

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“…Therefore, it is interesting that low levels of the Th1-stimulating cytokine IL-12 have been found in cord blood in children, who later develop RSV bronchiolitis [66]. Low IL-12 production has also been found in infants with severe RSV bronchiolitis [67].…”

Section: Obstructive Airway Diseases After Rsv Bronchiolitissupporting

confidence: 87%

Relationship between respiratory syncytial virus bronchiolitis and future obstructive airway diseases

Wennergren¹,

Kristjánsson²

2001

European Respiratory Journal

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Relationship between respiratory syncytial virus bronchiolitis and future obstructive airway diseases. G. Wennergren, S. Kristjánsson. #ERS Journals Ltd 2001. ABSTRACT: Evidence from a large number of prospective case-control studies shows that respiratory syncytial virus (RSV) bronchiolitis in infancy is often associated with recurrent wheezing and asthma during subsequent years. However, wheezing tends to diminish and most studies show no significant increase in wheezing compared to controls by school age or adolescence. An unresolved question is whether severe RSV infection during infancy causes the respiratory sequelae or inherent abnormalities predispose an infant to develop severe respiratory infection and sequelae, i.e. RSV is associated with the development of pulmonary sequelae.Studies on long-term outcome of RSV bronchiolitis are reviewed from an evidencebased perspective.The majority of prospective placebo-controlled studies do not show any long-term beneficial effects of corticosteroid treatment, i.e. the risk of subsequent wheezing is not diminished by the treatment. The evidence for an increased risk of allergic sensitization after RSV bronchiolitis is not nearly as strong as the evidence for an increased risk of subsequent wheezing. In fact, most studies do not show any significant increase in atopy after RSV bronchiolitis. This suggests that the increased risk of wheezing after RSV is not linked to an increased risk of atopy. There are some indications that infants who develop severe RSV and subsequent wheezing may have aberrations that predate the RSV infection.To decide whether respiratory syncytial virus bronchiolitis causes, or is associated with the respiratory sequelae (or with subsequent allergy), it will be necessary to conduct prospective, randomized studies, where the cytokine profile prior to bronchiolitis onset is known. Such studies should preferably include some form of intervention against respiratory syncytial virus. A more complete understanding of the risk factors for severe respiratory syncytial virus infection and the role of respiratory syncytial virus infection in the initiation of asthma is needed as a basis for large-scale and cost-effective programmes to prevent respiratory syncytial virus-related morbidity. Eur Respir J 2001; 18: 1044-1058. Respiratory syncytial virus (RSV) bronchiolitis is the most common, severe lower respiratory tract infection in infancy. It now seems well established that RSV bronchiolitis in infancy is associated with recurrent wheezing and asthma during the first decade of life. In some children, wheezing after early lower airway infection with RSV is transient, but in many of the children RSV-induced bronchiolitis represents the onset of asthma. In fact, there are results which indicate that severe RSV bronchiolitis in the young infant may shift the T-helper (Th)1/Th2 balance in favour of a Th2 cytokine pattern, leading to development of allergic sensitization and persistent asthma [1,2]. However, the association with risk of development of atopy...

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“…Particularly noteworthy in the present study is the increased myofibroblast hyperplasia induced by IL-18 neutralization in IL-12p40 Ϫ/Ϫ mice after RSV infection, and this may significantly contribute to the pathophysiology of reactive or chronic airway disease (63). As IL-12 protein levels (14,15) and IL-18 mRNA levels (23) are decreased in RSV-induced bronchiolitis, administration of exogenous IL-12 (35) and/or IL-18 may, in part, limit the Th2 predominant immune response and lung inflammation during RSV infection. The findings in this study suggest a compensatory role for IL-18 in Th0 cell commitment following RSV infection.…”

Section: Discussionmentioning

confidence: 65%

“…IL-12 is believed to be a central mediator in the development of the Th1 immune response while inhibiting the Th2 immune responses to either exogenous microbes or noninfectious Ags (13). RSV-induced bronchiolitis in infants is associated with reduced IL-12 levels in cord blood samples (14). Likewise, the levels of monocyte IL-12 production are inversely related to the duration of respiratory failure in RSV-induced bronchiolitis (15).…”

Section: R Espiratory Syncytial Virus (Rsv)mentioning

confidence: 99%

IL-12p40 and IL-18 Modulate Inflammatory and Immune Responses to Respiratory Syncytial Virus Infection

Wang

Bao

Rosenberger

et al. 2004

The Journal of Immunology

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Respiratory syncytial virus-induced bronchiolitis has been linked to the development of allergy and atopic asthma. IL-12 and possibly IL-18 are central mediators orchestrating Th1 and/or Th2 immune responses to infection. To determine a possible role for IL-12 in regulating the immune response to acute respiratory syncytial virus infection, IL-12p40 gene-targeted (IL-12p40−/−) and wild-type mice were intratracheally infected with respiratory syncytial virus, and lung inflammatory and immune responses were assessed. Lung inflammation and mucus production were increased in the airways of IL-12p40−/− mice as compared with those of wild-type mice, concurrent with increased levels of the Th2 effector cytokines IL-5 and IL-13. Respiratory syncytial virus clearance and levels of Th1 effector cytokine IFN-γ were not altered. Interestingly, IL-18, another mediator of IFN-γ production, was significantly increased in the lungs of IL-12p40−/− mice early during the course of infection. Abrogation of IL-18-mediated signaling in IL-12p40−/− mice further enhanced Th2 immune response and mucus production in the airways during respiratory syncytial virus infection but failed to modulate IFN-γ production or viral clearance. These findings implicate a role for IL-12 and IL-18 in modulating respiratory syncytial virus-induced airway inflammation distinct from that of viral clearance.

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Decreased interleukin-12 levels in umbilical cord blood in children who developed acute bronchiolitis

Cited by 58 publications

References 38 publications

IL-13-Induced Airway Hyperreactivity During Respiratory Syncytial Virus Infection Is STAT6 Dependent

IL-13-Induced Airway Hyperreactivity During Respiratory Syncytial Virus Infection Is STAT6 Dependent

Relationship between respiratory syncytial virus bronchiolitis and future obstructive airway diseases

IL-12p40 and IL-18 Modulate Inflammatory and Immune Responses to Respiratory Syncytial Virus Infection

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