IL-33 and ST2 as predictors of disease severity in children with viral acute lower respiratory infection

Portugal, Carolina Augusta Arantes; de Araújo Castro, Ítalo; Prates, Mirela Cristina Moreira; Gagliardi, Talita Bianca; Martins, Ronaldo Bragança; de Jesus, Bruna Laís Santos; de Souza Cardoso, Ricardo; da Silva, Marcus Vinícius Gomes; Aragon, Davi Casale; Arruda Neto, Eurico; Alves Filho, José Carlos Farias; Cunha, Fernando de Queiroz; Carlotti, Ana Paula de Carvalho Panzeri

BACKGROUND: Mechanisms influencing severity of acute lower respiratory infection (ALRI) in children are not established. We aimed to assess the role of inflammatory markers and respiratory viruses in ALRI severity. METHODS: Concentrations of interleukin(IL)-33, soluble suppression of tumorigenicity (sST)2, IL-1ß, tumor necrosis factor α, IL-4, IL-6 and IL- 8 and types of respiratory viruses were evaluated in children at the first and fifth days after hospital admission. Disease severity was defined as need for mechanical ventilation. RESULTS: Seventy-nine children <5 years-old were included; 33(41.8%) received mechanical ventilation. No associations between virus type, viral load or co-detections and severity of disease were observed. Detection of IL-33 and sST2 in nasopharyngeal aspirates (NPA) on admission were associated with higher risk for mechanical ventilation (RR = 2.89 and RR = 4.57, respectively). IL-6 and IL-8 concentrations were higher on Day 5 in mechanically ventilated children. IL-6 NPA concentrations decreased from Day 1 to Day 5 in children who did not receive mechanical ventilation. Increase in sST2 NPA concentrations from Day 1 to Day 5 was associated with longer hospital length of stay (p < 0.01). CONCLUSIONS: An exacerbated local activation of the IL-33/ST2 axis and persistently high sST2 concentrations over time were associated with severity of viral ALRI in children.