Different proinflammatory reactions in fatal and non-fatal enterovirus 71 infections: Implications for early recognition and therapy

Aim: The mechanism of pulmonary oedema, a life-threatening manifestation of enterovirus 71 (EV71) encephalitis, is unclear. Our aim was to assess the relationship of proinflammatory cytokines to EV71-related pulmonary oedema. Methods: Proinflammatory responses in 33 EV71 patients with various complications and 21 normal healthy children were measured using an enzyme-linked immunosorbent assay. Results: EV71 patients with both encephalitis and pulmonary oedema were found to have much higher levels of blood interleukin-6 (IL-6) (947 ± 1239 vs 4.9 ± 3.1 pg/ml, p = 0.0003), tumour necrosis factor-α (TNF-α) (22.4 ± 29.5 vs 5.3 ± 1.0 pg/ml, p = 0.0035), interleukin 1β (IL-1β) (48.4 ± 85.2 vs 4.9 ± 10.1 pg/ml, p = 0.01), white blood cell count (28.3 ± 7.6 vs 15.5 ± 6.8 10⁹/L, p ≤ 0.0001) and blood glucose (501 ± 186 vs 165 ± 117 mg/dL, p=0.0009) than patients with EV71 encephalitis alone. In fact, the cytokine levels in patients with encephalitis only or in those without complications were not significantly different from the levels found in normal children. The sensitivity, specificity, positive and negative predictive values of IL-6 > 70pg/ml for EV71 encephalitis with pulmonary oedema were all 100%. Conclusion: Patients with EV71-related encephalitis combined with pulmonary oedema were found to have significantly elevated levels of proinfiammatory cytokines and the best predictor for this complicated condition was found to be the level of serum IL-6.