Aumento de interleuquinas proinflamatorias y de cortisol plasmático en bronquiolitis por virus respiratorio sincicial: relación con la gravedad de la infección / Levels of inflammatory cytokines and plasma cortisol in respiratory syncytial virus bronchiolitis

Background: An increased inflammatory innate response may play a role in pathogenesis of respiratory syncytial virus (RSV) infection. Aim: To quantify pro-inflammatory cytokines (IL-6-IL-8, ÍL-2-P and TNF-a) in nasopharyngeal aspirate (NPA) and plasma, and plasma cortisol in previously healthy infants with RSV bronchiolitis. Patients and Methods: We studied 49 infants aged less than one year of age with RSV bronchiolitis and 25 healthy controls. Severity was defined using a previously described modified score. We quantified interleukins in NPA and plasma by flow cytometry and plasma cortisol by radioimmunoanalysis. Results: Among patients with RSV bronchiolitis, 25 were classified as severe and 24 as moderate or mild. Significantly higher levels ofIL-6 and IL-8 in NPA and plasma and IL-lfi in NPA were found in children classified as severe, when compared to those with moderate or mild disease and controls. There was a positive correlation between IL-6 and cortisol in plasma (r = 0,55; p < 0,0001) and both were correlated with the severity of the disease. Conclusions: RSV bronchiolitis severity was associated with higher levéis of inflammatory interleukins and plasma cortisol.

Correlação entre mediadores inflamatórios na secreção nasofaríngea e no soro de crianças com infecção do trato respiratório inferior por vírus sincicial respiratório e a gravidade da doença / Correlation between inflammatory mediators in the nasopharyngeal secretion and in the serum of children with lower respiratory tract infection caused by respiratory syncytial virus and disease severity

OBJETIVO: Avaliar se as concentrações dos mediadores inflamatórios (CCL5, soluble intercellular adhesion molecule type 1 [sICAM-1], TNF-α, IL-6 e IL-10) na secreção nasofaríngea e no soro de crianças com infecção do trato respiratório inferior (ITRI) por vírus sincicial respiratório (VSR) apresentam correlação com os marcadores clínicos de gravidade da doença. MÉTODOS: Entre julho de 2004 e dezembro de 2005, 30 crianças com idade inferior a três meses, diagnosticadas com ITRI por VSR e admitidas em uma UTI neonatal foram incluídas neste estudo. RESULTADOS: Houve uma correlação positiva significante entre a gravidade da doença na admissão hospitalar, determinada por um sistema de escore clínico modificado, e as concentrações de sICAM-1 e de IL-10 na secreção nasofaríngea e de IL-6 no soro dos pacientes. Houve também uma correlação positiva significante entre a concentração de IL-6 no soro e o tempo de oxigenoterapia e a duração da internação. CONCLUSÕES: As concentrações de sICAM-1 e IL-10 na secreção nasofaríngea e de IL-6 no soro determinadas na admissão poderiam ser usadas como marcadores de gravidade da ITRI por VSR. Os níveis de IL-6 determinados no soro na admissão também poderiam ser usados para predizer o prolongamento da oxigenoterapia e da duração da internação.

OBJECTIVE: To determine whether the concentrations of inflammatory mediators (CCL5, soluble intercellular adhesion molecule type 1 [sICAM-1], TNF-α, IL-6 and IL-10) in the nasopharyngeal secretion and in the serum of children with lower respiratory tract infection (LRTI) caused by respiratory syncytial virus (RSV) correlate with the clinical markers of disease severity. METHODS: Between July of 2004 and December of 2005, 30 children less than three months of age, diagnosed with LRTI caused by RSV and admitted to a neonatal ICU, were included in this study. RESULTS: The severity of disease at hospital admission, as determined with a modified clinical scoring system, presented a significant positive correlation with sICAM-1 and IL-10 concentrations in the nasopharyngeal secretion, as well as with IL-6 concentrations in the serum, of the patients. In addition, serum IL-6 concentrations presented a significant positive correlation with the duration of oxygen therapy and with the length of hospital stay. CONCLUSIONS: At hospital admission, the concentrations of sICAM-1 and IL-10 in the nasopharyngeal secretion, as well as the concentration of IL-6 in the serum, could be used as markers of severity in patients with LRTI caused by RSV. The serum levels of IL-6 determined at admission could also be used to predict prolonged oxygen supplementation and hospital stay.

Plasma endothelin-1 in infants and young children with acute bronchiolitis and viral pneumonia.

Respiratory syncytial virus (RSV) Infections that occur during the first three years of life have been demonstrated to be associated with the development of childhood asthma. The mechanism of virus-triggered airway inflammation Is not fully understood. Endothelin-1 is a potent bronchoconstrictor involved in many diseases including respiratory tract infections. Infants and young children diagnosed with either viral pneumonia or acute bronchiolitis, their age ranging between 2 months and 3 years, were recruited into this study. Nasopharyngeal aspirates were taken for detection of respiratory virus by antigen immunofluorescence stain, RT-PCR analysis and viral culture. Plasma endothelin-1 (ET-1) was measured by using a commercially available enzyme-linked immunosorbent assay (ELISA). Ten of the nineteen infants and children (52%) were positive for RSV infection, one co-infected with influenza A. Nine Infants (90%) were positive for RSV subtype A. There was only one infant with subtype B. One of the RSV negative individuals was positive for influenza A. In addition, we recruited 10 patients without chronic underlying or respiratory tract illness as controls. ET-1 levels were significantly increased in RSV infection compared to the controls (3.6 +/- 1.2 and 1.2 +/- 1 pg/ml, respectively (p < 0.05). In conclusion, infants and young children who are infected with RSV have an increase in circulating plasma endothelin-1. This in turn may contribute to the subsequent development of childhood asthma.

A primate model of respiratory syncytial virus infection.

To determine whether bonnet monkeys are susceptible to infection and disease due to respiratory syncytial virus (RSV), 4 juvenile bonnet monkeys (Macaca radiata) were inoculated with RSV intratracheally and sacrificed at 3, 5, 7 and 9 days post infection. RSV was cultured from pre-autopsy broncheoalveolar lavage fluid from all 4 animals with a peak titre of virus on day 9. Serum RSV neutralizing antibody was present by day 7. Animals developed tachypnoea and chest retractions by 5th day post infection and 2 animals had lobular pneumonia on chest radiography. The pathological changes were of a bronchovascular inflammation, interstitial pneumonia and alveolitis, akin to that seen in humans. These findings show that bonnet monkeys can be infected with RSV, and can develop immune response and clinical and pathological changes similar to those seen in human infants with RSV disease. Thus intractracheal RSV inoculation of juvenile bonnet monkeys appears to be a good model to study pathogenesis of RSV disease.