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

Abstract

A B S T R A C TBackground: 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.

An immune-based biomarker signature is associated with mortality in COVID-19 patients

“…sST2 serves as a soluble decoy receptor for IL-33, and its expression is enhanced by proinflammatory cytokines in human lung epithelial cells ( 85 ), in particular when neutrophilic inflammation is present ( 86 – 88 ). Moreover, sST2 has previously been shown to predict disease severity in children with acute viral lower respiratory tract infections ( 89 ). Together, these studies further suggest a prominent role for neutrophilic lung inflammation as a major contributor to poor outcome in COVID-19.…”

Host Inflammatory Response in Viral Lower Respiratory Tract Infections: Friend or Foe?

“…51 Similarly, another study found that IL-33 or ST2 levels in nasopharyngeal secretions were associated with the severity of acute LRTI in children <5 years (p<0.001). 52 The study also showed a higher risk of mechanical ventilation with a risk ratio of 2.89 (95% CI: 1.83-4.57) for IL-33 and a risk ratio of 4.57 (95% CI: 1.78-11.70) for soluble suppression of tumorigenicity 2. 52 Sinha summarized the need for further investigation to establish the mechanisms involved and determine whether IL-33 is involved in dysregulated inflammation and epithelial and endothelial dysfunction pathways.…”

“…52 The study also showed a higher risk of mechanical ventilation with a risk ratio of 2.89 (95% CI: 1.83-4.57) for IL-33 and a risk ratio of 4.57 (95% CI: 1.78-11.70) for soluble suppression of tumorigenicity 2. 52 Sinha summarized the need for further investigation to establish the mechanisms involved and determine whether IL-33 is involved in dysregulated inflammation and epithelial and endothelial dysfunction pathways. Additionally, there needs to be better understanding of the kinetics of IL-33, as well as better understanding in the molecular epidemiology of viral LRTI populations.…”

Role of ST2 as a biomarker of respiratory dysfunction after interstitial pneumonia

“…In the pulmonary fi eld, IL-33/ST2 axis is involved in the genesis and development of numerous illnesses: higher sST2 serum and broncho-alveolar lavage concentrations have been noted in patients with acute eosinophilic pneumonia [15], in allergic diseases as asthma [16], chronic obstructive pulmonary disease [17], allergic rhinitis [18], and non-allergic pulmonary diseases [19], chest trauma injuries [20], ARDS [21,22]. Moreover, a recent study on pediatric population has shown as a exacerbated IL-33/ST2 axis activity and persistently high concentration of sST2 can be correlated with acute viral low respiratory infections [23].…”