Abstract
Enterovirus 71 (EV71) brainstem encephalitis (BE) is divided into—uncomplicated BE, autonomic nervous system (ANS) dysregulation, and pulmonary edema (PE)—based on cytokine-mediated severe systemic and central nervous system (CNS) inflammatory responses. Minocycline has been found to have anti-inflammatory and immunomodulatory properties in infectious and inflammatory neurological disease models. The effects of minocycline on EV71 infection were studied in vitro and in vivo experiments. The minocycline treatment (100–300 μg/mL) on cytokine expressions and viral replications were investigated in rhabdomyosarcoma (RD), U-87MG, and THP-1 cells. The mouse-adapted-EV71 strain (MP4)-infected 7-day-old ICR mice model was used to explore the anti-inflammatory and antiviral effects of minocycline (1 and 5 μg/g) for the treatment of EV71 infection. In in vitro, minocycline reduced cytopathic effects (CPEs), viral protein expressions, viral titers, the levels of interleukin (IL)-6 and IL-8 and relative mRNA expressions of IL-12p40, IL-1β, and tumor necrosis factor (TNF) after EV71 infection. The levels of TNF, IL-1β, IL-6, and IL-8 decreased with a single dose of minocycline in EV71-infected THP-1 cells. Double-dose minocycline treatment demonstrated more effective reduction in cytokines. In the MP4-infected animal model, clinical scores, mortality rates and viral titers in various brain tissues were decreased evidently after double-dose minocycline treatment. Minocycline inhibited IL-6 and granulocyte colony-stimulating factor (G-CSF) in plasma and TNF in the cerebellum. Minocycline has properties that enable it to function both as an anti-inflammatory and antiviral agent in EV71 infection. These results evidence its potential usefulness in clinical treatment.
| Original language | English |
|---|---|
| Article number | 109271 |
| Journal | Biomedicine and Pharmacotherapy |
| Volume | 118 |
| DOIs | |
| Publication status | Published - 2019 Oct 1 |
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All Science Journal Classification (ASJC) codes
- Pharmacology
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Anti-inflammatory and antiviral effects of minocycline in enterovirus 71 infections. / Liao, Yu Ting; Wang, Shih-Min; Chen, Shun Hua.
In: Biomedicine and Pharmacotherapy, Vol. 118, 109271, 01.10.2019.Research output: Contribution to journal › Article
TY - JOUR
T1 - Anti-inflammatory and antiviral effects of minocycline in enterovirus 71 infections
AU - Liao, Yu Ting
AU - Wang, Shih-Min
AU - Chen, Shun Hua
PY - 2019/10/1
Y1 - 2019/10/1
N2 - Enterovirus 71 (EV71) brainstem encephalitis (BE) is divided into—uncomplicated BE, autonomic nervous system (ANS) dysregulation, and pulmonary edema (PE)—based on cytokine-mediated severe systemic and central nervous system (CNS) inflammatory responses. Minocycline has been found to have anti-inflammatory and immunomodulatory properties in infectious and inflammatory neurological disease models. The effects of minocycline on EV71 infection were studied in vitro and in vivo experiments. The minocycline treatment (100–300 μg/mL) on cytokine expressions and viral replications were investigated in rhabdomyosarcoma (RD), U-87MG, and THP-1 cells. The mouse-adapted-EV71 strain (MP4)-infected 7-day-old ICR mice model was used to explore the anti-inflammatory and antiviral effects of minocycline (1 and 5 μg/g) for the treatment of EV71 infection. In in vitro, minocycline reduced cytopathic effects (CPEs), viral protein expressions, viral titers, the levels of interleukin (IL)-6 and IL-8 and relative mRNA expressions of IL-12p40, IL-1β, and tumor necrosis factor (TNF) after EV71 infection. The levels of TNF, IL-1β, IL-6, and IL-8 decreased with a single dose of minocycline in EV71-infected THP-1 cells. Double-dose minocycline treatment demonstrated more effective reduction in cytokines. In the MP4-infected animal model, clinical scores, mortality rates and viral titers in various brain tissues were decreased evidently after double-dose minocycline treatment. Minocycline inhibited IL-6 and granulocyte colony-stimulating factor (G-CSF) in plasma and TNF in the cerebellum. Minocycline has properties that enable it to function both as an anti-inflammatory and antiviral agent in EV71 infection. These results evidence its potential usefulness in clinical treatment.
AB - Enterovirus 71 (EV71) brainstem encephalitis (BE) is divided into—uncomplicated BE, autonomic nervous system (ANS) dysregulation, and pulmonary edema (PE)—based on cytokine-mediated severe systemic and central nervous system (CNS) inflammatory responses. Minocycline has been found to have anti-inflammatory and immunomodulatory properties in infectious and inflammatory neurological disease models. The effects of minocycline on EV71 infection were studied in vitro and in vivo experiments. The minocycline treatment (100–300 μg/mL) on cytokine expressions and viral replications were investigated in rhabdomyosarcoma (RD), U-87MG, and THP-1 cells. The mouse-adapted-EV71 strain (MP4)-infected 7-day-old ICR mice model was used to explore the anti-inflammatory and antiviral effects of minocycline (1 and 5 μg/g) for the treatment of EV71 infection. In in vitro, minocycline reduced cytopathic effects (CPEs), viral protein expressions, viral titers, the levels of interleukin (IL)-6 and IL-8 and relative mRNA expressions of IL-12p40, IL-1β, and tumor necrosis factor (TNF) after EV71 infection. The levels of TNF, IL-1β, IL-6, and IL-8 decreased with a single dose of minocycline in EV71-infected THP-1 cells. Double-dose minocycline treatment demonstrated more effective reduction in cytokines. In the MP4-infected animal model, clinical scores, mortality rates and viral titers in various brain tissues were decreased evidently after double-dose minocycline treatment. Minocycline inhibited IL-6 and granulocyte colony-stimulating factor (G-CSF) in plasma and TNF in the cerebellum. Minocycline has properties that enable it to function both as an anti-inflammatory and antiviral agent in EV71 infection. These results evidence its potential usefulness in clinical treatment.
UR - http://www.scopus.com/inward/record.url?scp=85070010827&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85070010827&partnerID=8YFLogxK
U2 - 10.1016/j.biopha.2019.109271
DO - 10.1016/j.biopha.2019.109271
M3 - Article
C2 - 31377467
AN - SCOPUS:85070010827
VL - 118
JO - Biomedicine and Pharmacotherapy
JF - Biomedicine and Pharmacotherapy
SN - 0753-3322
M1 - 109271
ER -