Effects of echinocandins on cytokine/chemokine production by human monocytes activated by infection with Candida glabrata or by lipopolysaccharide.
Serious Candida glabrata infections, which can be difficult to treat, are often treated with echinocandins. We compared in vitro the effects of high and low concentrations of 3 echinocandins (micafungin [MCF], caspofungin [CAS], and anidulafungin [ANF]), voriconazole (VRC), and amphotericin B (AmB), singly and VRC in combination with MCF, CAS, and ANF, on the production of cytokines/chemokines by human monocyte-derived macrophages (MDM). MDM were activated by infection with C. glabrata or lipopolysaccharide (LPS). Luminex multi-analyte microsphere technology was used for cytokine/chemokine analysis. Concentrations of cytokines/chemokines were significantly elevated following activation by infection or LPS. Treatment with high concentrations of echinocandins, singly or in combination with VRC, was most effective in lowering the elevated cytokine/chemokine levels. This effect occurred only with MDM activated by infection with C. glabrata and not with LPS. Treatment with VRC or AmB alone had little or no effect on cytokine/chemokine levels. In severe C. glabrata infection associated with very high concentrations of dysregulated cytokines/chemokines, echinocandins, singly or in combination with VRC, may decrease cytokine/chemokine concentrations and thus may improve host survival.
Stratton Veterans Affairs Medical Center, Albany, NY 12208, USA. Aldona.Baltch@med.va.gov
Aldona L
AL
Baltch
David A
DA
Lawrence
William J
WJ
Ritz
Nancy J
NJ
Andersen
Lawrence H
LH
Bopp
Phyllis B
PB
Michelsen
Cynthia J
CJ
Carlyn
Raymond P
RP
Smith
D000935:Antifungal Agents / Q000494:pharmacology*; D041221:Candida glabrata / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology / Q000378:metabolism; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis*; D054714:Echinocandins / Q000494:pharmacology*; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology*; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology*
D000935:Antifungal Agents; D018925:Chemokines; D016207:Cytokines; D054714:Echinocandins; D008070:Lipopolysaccharides