Glycyrrhizin inhibits highly pathogenic H5N1 influenza A virus-induced pro-inflammatory cytokine and chemokine expression in human macrophages.
Hypercytokinaemia is thought to contribute to highly pathogenic H5N1 influenza A virus disease. Glycyrrhizin is known to exert immunomodulatory and anti-inflammatory effects and therefore a candidate drug for the control of H5N1-induced pro-inflammatory gene expression. Here, the effects of an approved parenteral glycyrrhizin preparation were investigated on H5N1 virus replication, H5N1-induced pro-inflammatory responses, and H5N1-induced apoptosis in human monocyte-derived macrophages. Glycyrrhizin 100 μg/ml, a therapeutically achievable concentration, impaired H5N1-induced production of CXCL10, interleukin 6, and CCL5 and inhibited H5N1-induced apoptosis but did not interfere with H5N1 replication. Global inhibition of immune responses may result in the loss of control of virus replication by cytotoxic immune cells including natural killer cells and cytotoxic CD8(+) T-lymphocytes. Notably, glycyrrhizin concentrations that inhibited H5N1-induced pro-inflammatory gene expression did not affect cytolytic activity of natural killer cells. Since H5N1-induced hypercytokinaemia is considered to play an important role within H5N1 pathogenesis, glycyrrhizin may complement the arsenal of potential drugs for the treatment of H5N1 disease.
Michaelis
Martin
M
Institut für Medizinische Virologie, Klinikum der JW Goethe-Universität, Frankfurt am Main, Germany.
Geiler
Janina
J
Naczk
Patrizia
P
Sithisarn
Patchima
P
Ogbomo
Henry
H
Altenbrandt
Behric
B
Leutz
Anke
A
Doerr
Hans Wilhelm
HW
Cinatl
Jindrich
J
D017209:Apoptosis; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology* / Q000502:physiology; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology* / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects
C483024:CCL5 protein, human; C114753:CXCL10 protein, human; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D016207:Cytokines; C508600:IL6 protein, human; D007155:Immunologic Factors; D015850:Interleukin-6; D019695:Glycyrrhizic Acid
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