Key result
Norepinephrine and epinephrine significantly enhanced the percentage of EV71-infected cells and virus titers in vitro, correlating with elevated plasma catecholamine levels in patients with severe EV71 complications.
Why the study?
Do norepinephrine and epinephrine enhance the infectivity of Enterovirus 71 in vitro?
Do norepinephrine and epinephrine enhance the infectivity of Enterovirus 71 in vitro?
Absolute Event Rate: 62.9% vs 39.4%
p-value: p=<0.05
Catecholamines (norepinephrine and epinephrine) enhance EV71 infectivity in vitro, suggesting a role in the pathogenesis of severe EV71 brainstem encephalitis complicated by autonomic nervous system dysregulation.
May link catecholamines to EV71 severity; hypothesis-generating and should not change practice.
BACKGROUND: Enterovirus 71 (EV71) infections may be associated with neurological complications, including brainstem encephalitis (BE). Severe EV71 BE may be complicated with autonomic nervous system (ANS) dysregulation and/or pulmonary edema (PE). ANS dysregulation is related to the overactivation of the sympathetic nervous system, which results from catecholamine release. OBJECTIVE: The aims of this study were to explore the effects of catecholamines on severe EV71 infection and to investigate the changes in the percentages of EV71-infected cells, virus titer, and cytokine production on the involvement of catecholamines. STUDY DESIGN: Plasma levels of norepinephrine (NE) and epinephrine (EP) in EV71-infected patients were measured using an enzyme-linked immunoassay. The expression of adrenergic receptors (ADRs) on RD, A549, SK-N-SH, THP-1, Jurkat and human peripheral blood mononuclear cells (hPBMCs) were detected using flow cytometry. The percentages of EV71-infected cells, virus titer, and cytokine production were investigated after treatment with NE and EP. RESULTS: The plasma levels of NE and EP were significantly higher in EV71-infected patients with ANS dysregulation and PE than in controls. Both α1A- and β2-ADRs were expressed on A549, RD, SK-N-SH, HL-60, THP-1, Jurkat cells and hPBMCs. NE treatment elevated the percentages of EV71-infected cells to 62.9% and 22.7% in THP-1 and Jurkat cells, respectively. Via treatment with EP, the percentages of EV71-infected cells were increased to 64.6% and 26.9% in THP-1 and Jurkat cells. The percentage of EV71-infected cells increased upon NE or EP treatment while the α- and β-blockers reduced the percentages of EV71-infected cells with NE or EP treatment. At least two-fold increase in virus titer was observed in EV71-infected A549, SK-N-SH and hPBMCs after treatment with NE or EP. IL-6 production was enhanced in EV71-infected hPBMCs at a concentration of 102 pg/mL NE. CONCLUSION: The plasma levels of NE and EP elevated in EV71-infected patients with ANS dysregulation and PE. Both NE and EP enhanced the percentages of infected cells and virus titers in EV71 infection in vitro. NE and EP may play a role in the pathogenesis of EV71 BE complicated with ANS dysregulation and PE.
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Liao et al. (2015) studied Enterovirus 71 (EV71) infection (n=27). Norepinephrine and Epinephrine vs. EV71 infection without catecholamine treatment was evaluated on Percentage of EV71-infected THP-1 cells (p=<0.05). Norepinephrine and epinephrine significantly enhanced the percentage of EV71-infected cells and virus titers in vitro, correlating with elevated plasma catecholamine levels in patients with severe EV71 complications.
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