Outbreaks of Human Enterovirus 71 (EV71) are often reported in Asia. EV71 is responsible for syndromes like hand-foot and mouth disease, but is also involved in pulmonary edema (PE) and in neurological complications, like brainstem encephalitis (BE) and autonomic nervous system dysregulation (ANS).
During cases of EV71 associated encephalitis, an elevated plasma level of epinephrine and norepinephrine was observed, raising the issue of interconnections between catecholamines and EV 71 infection. The authors have investigated the impact of catecholamines on EV 71 infection and vice-versa. They confirmed elevated plasma levels of epinephrine and norepinephrine in patients with BE compared to controls. The difference was more notable with norepinephrine. Catecholamine levels were even higher in BE complicated with ANS and PE than in uncomplicated BE.
The effects of epinephrine and norepinephrine on infection were studied. The authors used immune progenitor cell lines expressing α1A and β2 adrenergic receptors such as THP-1 monocytes cell line, Jurkat lymphocytes cell line and HL-60 myeloid cell line. Appropriate stimuli induced their differentiation into immune cells which increased the proportion of infected cells when they were exposed to EV71.
Norepinephrine or epinephrine treatment was able to further enhance the infection of differentiated cells of human peripheral blood mononuclear cells (PBMC) and of pulmonary (A549) and neuroblastoma (SK-N-SH) cell lines as well. In contrast, the rate of infection was lower when adrenergic receptors were blocked by using a neutralizing antibody.
Infected human PBMC treated with epinephrine or norepinephrine showed in increase in IL-6 production. However, the production of other cytokines, such as IL-10, IL-1β, IL-8 and IL-12p70 was unaffected.
These data suggest that catecholamines enhance the infection with EV71. During brainstem encephalitis, an increased release of epinephrine and norepinephrine is observed, resulting in a vicious circle where EV71 enhances its own infection.
Blocking adrenergic receptors with neutralizing antibodies resulted in a reduced infection. Whether blocking these receptors would be useful to avoid the worsening of brainstem encephalitis deserves further investigation.