Literature data support the notion that uraemia is associated with an acquired immune deficiency which involves both cellular and humoral immunity, with the degree of impairment related to the duration of the uraemic state. According to these studies, microbial phagocytosis and intracellular killing result generally impaired in polymorphonuclear cells (PMNs) from uraemic patients, as a consequence of a reduced ability to generate superoxide in response to stimuli as well as impaired chemotaxis and degranulation. Since synergism between phagocytic cells and antimicrobial drugs may be crucial for successful therapy, the purpose of this study was to evaluate the potential PMN-caspofungin interaction in eradicating Candida albicans and C.glabrata by testing both the phagocytic and fungicidal activities of PMNs from patients under chronic haemodialysis treatment (HDs) compared to those of PMNs from healthy subjects (HSs), used as controls. PMNs were separated from venous blood samples of 66 HDs and 30 HSs and measurement of phagocytic and intracellular fungicidal activities of HD-PMNs and HS-PMNs was performed in presence of caspofungin at the MIC. Caspofungin free-controls were also included. Based on our in vitro results, HD-PMNs were able to phagocytose yeast cells, with a phagocytosis pattern quite similar to that detected in HS-PMNs. On the other hand, a progressive decline in the fungicidal activity of HD-PMNs was confirmed. As the majority of systemically acting antifungal drugs, caspofungin did not significantly improve the phagocytic activity. Conversely, the fungicidal activity of HD-PMNs was significantly potentiated by caspofungin against both C.albicans and C.glabrata. Our current data provide evidence that caspofungin is able to restore the depressed intracellular killing of PMNs, through a synergistic effect with PMNs towards C.albicans and C.glabrata and may constitute effective therapeutic option for invasive fungal infection treatment in patients with altered phagocyte-dependent innate immunity.
Caspofungin improves chronic haemodialysis patient phagocyte response against Candida albicans and C.glabrata
ALLIZOND, VALERIA;BANCHE, Giuliana;SCALAS, Daniela;MERLINO, Chiara;MANDRAS, Narcisa;ROANA, Janira;TULLIO, Viviana Cristina;CUFFINI, Annamaria
2011-01-01
Abstract
Literature data support the notion that uraemia is associated with an acquired immune deficiency which involves both cellular and humoral immunity, with the degree of impairment related to the duration of the uraemic state. According to these studies, microbial phagocytosis and intracellular killing result generally impaired in polymorphonuclear cells (PMNs) from uraemic patients, as a consequence of a reduced ability to generate superoxide in response to stimuli as well as impaired chemotaxis and degranulation. Since synergism between phagocytic cells and antimicrobial drugs may be crucial for successful therapy, the purpose of this study was to evaluate the potential PMN-caspofungin interaction in eradicating Candida albicans and C.glabrata by testing both the phagocytic and fungicidal activities of PMNs from patients under chronic haemodialysis treatment (HDs) compared to those of PMNs from healthy subjects (HSs), used as controls. PMNs were separated from venous blood samples of 66 HDs and 30 HSs and measurement of phagocytic and intracellular fungicidal activities of HD-PMNs and HS-PMNs was performed in presence of caspofungin at the MIC. Caspofungin free-controls were also included. Based on our in vitro results, HD-PMNs were able to phagocytose yeast cells, with a phagocytosis pattern quite similar to that detected in HS-PMNs. On the other hand, a progressive decline in the fungicidal activity of HD-PMNs was confirmed. As the majority of systemically acting antifungal drugs, caspofungin did not significantly improve the phagocytic activity. Conversely, the fungicidal activity of HD-PMNs was significantly potentiated by caspofungin against both C.albicans and C.glabrata. Our current data provide evidence that caspofungin is able to restore the depressed intracellular killing of PMNs, through a synergistic effect with PMNs towards C.albicans and C.glabrata and may constitute effective therapeutic option for invasive fungal infection treatment in patients with altered phagocyte-dependent innate immunity.
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