IMMUNOLOGICAL EFFECTS OF AMPHOTERICIN-B AND LIPOSOMAL AMPHOTERICIN-B ON SPLENOCYTES FROM IMMUNE-NORMAL AND IMMUNE-COMPROMISED MICE

The immunological effects of amphotericin B and liposomal amphotericin B were studied in vitro by measuring B- and T-lymphocyte proliferatio n on splenocytes from immune-normal, cyclosporine-compromised, and cyc lophosphamide-compromised mice. Cellular viability of cells from immun e-normal mice was also evaluated. The concentrations used (0, 0.5, 1, 2, 4, 8, and 16 mu g/ml) encompassed clinically relevant doses. Amphot ericin B consistently reduced the abilities of B cells and T cells to proliferate, especially when administered at higher than clinically re levant doses. Direct cytotoxicity probably played only a minor role, s ince viability studies showed that, compared with its liposomal analog , amphotericin B reduced the number of viable cells by no more than 10 %. Clinically relevant doses of liposomal amphotericin B (A. S. Janoff , L. T. Boni, M. C. Popescu, S. R. Minchey, P. R. Cullis, T. D. Madden , T. Tarashi, S. M. Gruner, E. Shyamsunder, M. W. Tate, R. Mendelsohn, and D. Bonner, Proc. Natl. Acad. Sci. USA 85:6122-6126, 1988; R. Meht a, G. Lopez-Berestein, R. Hopfer, K. Mills, and R. I,. Juliano, Biochi m. Biophys. Acta 770:230-234, 1984) did not inhibit any of the immune parameters examined. Liposomes may, therefore, be a useful means of de livering more drug to a host infected with a fungal organism without f urther compromising the patient's already suppressed immune system.