Suppression of interleukin-6 increases enterovirus A71 lethality in mice

Figures

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  Fig. 1. EV-A71 infection increases serum and brain IL-6 levels of mice. IL-6 levels in the sera (a) and brains (b) of mice, which were mock-infected or infected with EV-A71 for the indicated days, are shown. Data show means + SEM (error bars) of ≥5 samples per group. **P < 0.01 and ***P < 0.001

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  Fig. 2. Absence of IL-6 increases the disease severity, mortality, tissue damage, and tissue viral loads of EV-A71-infected mice. The disease severity (a) and survival (b) of infected wild-type mice (black symbols or WT; n = 19) and infected IL-6 −/− mice (white symbols; n = 11) were monitored for 30 days. (c) Spinal cords of mock-infected or infected wild-type and IL-6 −/− mice were harvested 10 days after infection, sectioned, and stained with hematoxylin-eosin. The motor horn of lumbar region is shown. Data are representative of at least 3 samples from two independent experiments. (d) Viral titers in the indicated tissues of wild-type mice (WT; black circles) and IL-6 −/− mice (white circles) collected on 5 or 7 days after infection are shown. Data show means ± SEM (error bars) in panel a and 6–7 samples per data point in panel d. *P < 0.05 and **P < 0.01 compared between wild-type and IL-6 −/− mouse groups at the indicated time

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  Fig. 3. Absence of IL-6 reduces the virus-specific, neutralizing antibody response in the serum of EV-A71-infected mice. The neutralizing antibody titers in sera of wild-type (WT) mice and IL-6 −/− mice infected with virus for 10 days are shown. Each symbol on the scatter gram represents an individual sample, and the black horizontal line represents the mean value for wild-type mice. *P < 0.05

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  Fig. 4. The effect of IL-6 knockout on tissue lymphocyte numbers in EV-A71-infected mice. The numbers of CD19+ cells (a and d), CD4+ cells (b and e), and CD8+ cells (c and f) in the spleens (a to c) and brains (d to f) of wild-type (WT) mice and IL-6 −/− mice, which were mock-infected (−) or infected with EV-A71 (+) for 10 days, are shown. Data show means + SEM (error bars) of 5 samples per group. *P < 0.05 and **P < 0.01

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  Fig. 5. The effects of anti-IL-6 antibody treatment on the serum IL-6 level, survival rate, and tissue viral load of infected wild-type mice. Infected wild-type mice were treated with control or anti-IL-6 antibody on days 0 and 2 after infection and monitored for serum IL-6 levels (a), survival rates (b), and day-6 lung viral loads (c). Infected wild-type mice were treated with antibody on days 2 and 4 after infection (d) or on days 4 and 6 after infection (e) and monitored for survival rates. Data show means + SEM (error bars) of 3–4 samples per group in panel a, 8–9 mice per group in panel b, 5–6 samples per group in panel c, 9–10 mice per group in panel d, and 6–7 mice per group in panel e. *P < 0.05, **P < 0.01, and ***P < 0.001 compared between indicated groups or wild-type and IL-6−/− mouse groups