Candin family antifungal agent micafungin (FK463) modulates the inflammatory cytokine production stimulated by lipopolysaccharide in THP-1 cells.
Systemic inflammatory response syndrome (SIRS) and sepsis have been considered forms of hypercytokinemia in critically ill patients and immunocompromized hosts. It has been reported that some antimicrobial agents, including antifungal agents, not only have an antibiotic effect, but also they affect the host's immunological response. Immunofunctional cells, including monocytes and macrophages, were examined to determine whether they are influenced by the newly synthesized candin family antifungal agent micafungin (MCFG) using the human monocytic cell line THP-1 stimulated with lipopolysaccharide (LPS) as a model of hypercytokinetic conditions. LPS-induced production of TNF-alpha (tumor necrosis factor-alpha) and interleukin-8 (IL-8) in THP-1 cells was significantly suppressed dose-dependently by MCFG, although high concentrations of MCFG may reach toxic levels. It was clarified that MCFG inhibits the LPS-induced expression of TNF-alpha in THP-1 cells at the mRNA (messenger ribonucleic acid) level. In conclusion, administration of MCFG had an immunomodulatory effect on the host by reducing levels of TNF-alpha and IL-8. The effectiveness of MCFG in modulating hypercytokinemia is due not only to its direct antifungal effect, but also to the modulation of cytokine production in macrophages that regulates immunological activity and inflammation.
Kinoshita
Keiichi
K
First Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
Iwasaki
Hiromichi
H
Uzui
Hiroyasu
H
Ueda
Takanori
T
D000935:Antifungal Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D054714:Echinocandins; D015725:Fluconazole / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D055666:Lipopeptides; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008074:Lipoproteins / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D000077551:Micafungin; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D000935:Antifungal Agents; D004338:Drug Combinations; D054714:Echinocandins; D016209:Interleukin-8; D055666:Lipopeptides; D008070:Lipopolysaccharides; D008074:Lipoproteins; D010456:Peptides, Cyclic; D012333:RNA, Messenger; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D015725:Fluconazole; D000077551:Micafungin