Interleukin-18 binding protein in infants and children hospitalized with pneumonia in low-resource settings

Pneumonia is the leading infectious cause of death in children, with especially high mortality in low- and middle-income countries. Interleukin-18 binding protein (IL-18BP) is a natural antagonist of the pro-inflammatory cytokine interleukin-18 and is elevated in numerous autoimmune conditions and infectious diseases. We conducted a prospective cohort study to determine the association between admission IL-18BP levels and clinical severity among children admitted to two hospitals in Uganda for hypoxemic pneumonia. A total of 42 children (median age of 1.2 years) were included. IL-18BP levels were higher in patients with respiratory distress, including chest indrawing (median 15 ng/mL (IQR 9.8–18) versus 4.5 ng/mL (IQR 3.8–11) without chest indrawing, P = 0.0064) and nasal flaring (median 15 ng/mL (IQR 9.7–19) versus 11 ng/mL (IQR 5.4–14) without nasal flaring, P = 0.034). IL-18BP levels were positively correlated with the composite clinical severity score, Pediatric Early Death Index for Africa (PEDIA-e, ρ = 0.46, P = 0.0020). Patients with IL-18BP > 14 ng/mL also had slower recovery times, including time to sit (median 0.69 days (IQR 0.25–1) versus 0.15 days (IQR 0.076–0.36) with IL-18BP < 14 ng/mL, P = 0.036) and time to fever resolution (median 0.63 days (IQR 0.16–2) versus 0.13 days (IQR 0–0.42), P = 0.016). In summary, higher IL-18BP levels were associated with increased disease severity and prolonged recovery times in Ugandan children with pneumonia.