Abstract
BackgroundEnterovirus A71 (EV-A71) infection can induce fatal encephalitis in young children. Clinical reports show that interleukin-6 (IL-6) levels in the serum and cerebrospinal fluid of infected patients with brainstem encephalitis are significantly elevated. We used a murine model to address the significance of endogenous IL-6 in EV-A71 infection.ResultsEV-A71 infection transiently increased serum and brain IL-6 protein levels in mice. Most importantly, absence of IL-6 due to gene knockout or depletion of IL-6 using neutralizing monoclonal antibody enhanced the mortality and tissue viral load of infected mice. Absence of IL-6 increased the damage in the central nervous system and decreased the lymphocyte and virus-specific antibody responses of infected mice.ConclusionsEndogenous IL-6 functions to clear virus and protect the host from EV-A71 infection. Our study raises caution over the use of anti-IL-6 antibody or pentoxifylline to reduce IL-6 for patient treatment.
Highlights
Enterovirus A71 (EV-A71) infection can induce fatal encephalitis in young children
These results show that the significant increases of mouse serum and brain IL-6 levels induced by EV-A71 infection were gradually declined from day 4 p.i
We found transiently elevated serum and brain IL-6 levels, which reached peaks on day 2 p.i. and gradually declined from day 4 p.i., in 14-day-old C57BL/6J mice infected with 3 × 105 plaque forming units (PFU)/mouse of EV-A71 strain M2, which has been adapted in mice [34] and induced a mortality rate of 37%
Summary
Enterovirus A71 (EV-A71) infection can induce fatal encephalitis in young children. Clinical reports show that interleukin-6 (IL-6) levels in the serum and cerebrospinal fluid of infected patients with brainstem encephalitis are significantly elevated. Enterovirus A71 (EV-A71) is a neurotropic picornavirus transmitted by the fecal-oral route. It can infect the human central nervous system (CNS) to induce neurological manifestations, such as aseptic meningitis, encephalomyelitis, and brainstem encephalitis, especially in young children [1,2,3,4]. Previous clinical studies showed that the levels of serum cytokines, including interleukin (IL)-6, IL-1β, IL10, IL-13, and tumor necrosis factor alpha (TNF-α), in EV-A71-infected patients with both brainstem
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