Different proinflammatory reactions in fatal and non-fatal enterovirus 71 infections: implications for early recognition and therapy.
OBJECTIVE
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-alpha (TNF-alpha) (22.4 +/- 29.5 vs 5.3 +/- 1.0 pg/ml, p = 0.0035), interleukin Ibeta (IL-1beta) (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 10(9)/L, p > or = 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 > 70 pg/ml for EV71 encephalitis with pulmonary oedema were all 100%.


CONCLUSIONS
Patients with EV71-related encephalitis combined with pulmonary oedema were found to have significantly elevated levels of proinflammatory cytokines and the best predictor for this complicated condition was found to be the level of serum IL-6.
Lin
T Y
TY
Department of Pediatrics, Chang Gung Children's Hospital, Linkou, Taiwan.
Chang
L Y
LY
Huang
Y C
YC
Hsu
K H
KH
Chiu
C H
CH
Yang
K D
KD
D000704:Analysis of Variance; D001786:Blood Glucose / Q000032:analysis; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood*; D018792:Encephalitis, Viral / Q000150:complications / Q000175:diagnosis* / Q000401:mortality* / Q000628:therapy; D004769:Enterovirus Infections / Q000150:complications / Q000175:diagnosis* / Q000401:mortality* / Q000628:therapy; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007223:Infant; D018836:Inflammation Mediators / Q000097:blood*; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007958:Leukocyte Count; D008297:Male; D011237:Predictive Value of Tests; D011336:Probability; D011379:Prognosis; D011654:Pulmonary Edema / Q000150:complications / Q000175:diagnosis* / Q000401:mortality*; D018570:Risk Assessment; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D001786:Blood Glucose; D016207:Cytokines; D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha