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 proliferation on splenocytes from immune-normal, cyclosporine-compromised, and cyclophosphamide-compromised mice. Cellular viability of cells from immune-normal mice was also evaluated. The concentrations used (0, 0.5, 1, 2, 4, 8, and 16 micrograms/ml) encompassed clinically relevant doses. Amphotericin B consistently reduced the abilities of B cells and T cells to proliferate, especially when administered at higher than clinically relevant doses. Direct cytotoxicity probably played only a minor role, since 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. Mehta, G. Lopez-Berestein, R. Hopfer, K. Mills, and R. L. Juliano, Biochim. Biophys. Acta 770:230-234, 1984) did not inhibit any of the immune parameters examined. Liposomes may, therefore, be a useful means of delivering more drug to a host infected with a fungal organism without further compromising the patient's already suppressed immune system.
Schindler
J J
JJ
Department of Animal, Dairy and Veterinary Science, Utah State University, Logan 84322-5600.
Warren
R P
RP
Allen
S D
SD
Jackson
M K
MK
D000666:Amphotericin B / Q000008:administration & dosage* / Q000494:pharmacology*; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D002470:Cell Survival / Q000187:drug effects; D003520:Cyclophosphamide / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008081:Liposomes; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000494:pharmacology; D012680:Sensitivity and Specificity; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D013268:Stimulation, Chemical; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*
D004337:Drug Carriers; D007166:Immunosuppressive Agents; D008081:Liposomes; D008934:Mitogens; D000666:Amphotericin B; D016572:Cyclosporine; D003520:Cyclophosphamide