Influence of six antifungal agents on the chemiluminescence response of mouse spleen cells

Abstract

The luminol-enhanced chemiluminescence (CL) assay is a measure of the early events of phagocytosis, leukocyte activation, and immune cell interactions. Reduction in the CL response of immune cells may be indicative of an inhibition of the immune response. This study was undertaken to examine the effects of antifungal agents tested at concentrations above and below therapeutically achievable levels on the CL response of mouse spleen cells. The effects of six antifungal agents--amphotericin B, ketoconazole, miconazole, 5-fluorocytosine, Bay-n-7133, and ICI 153,066--were studied. Changes in the CL response were assessed in terms of peak intensity and area under the intensity-time curve compared with appropriate diluent controls for each drug. Only amphotericin B and ketoconazole caused statistically significant lowering of the peak intensity at levels that are therapeutically attainable (mean peak plasma levels of 2 to 4 and 3.5 to 16 micrograms/ml, respectively). Although amphotericin B and ketoconazole caused reduction in the CL response, removal of the unbound drug in the preparation by centrifugation, washing, and suspension of cells in fresh drug-free medium resulted in a return of CL activity equivalent to the activity observed in cells not exposed to these agents. These results suggest that amphotericin B and ketoconazole at therapeutic concentrations may cause a reduction in immune cell antimicrobial activity; the clinical significance of these observations remains to be determined.