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. 1993 Dec;37(12):2716–2721. doi: 10.1128/aac.37.12.2716

Immunological effects of amphotericin B and liposomal amphotericin B on splenocytes from immune-normal and immune-compromised mice.

J J Schindler 1, R P Warren 1, S D Allen 1, M K Jackson 1
PMCID: PMC192788  PMID: 8109941

Abstract

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andreoli T. E., Monahan M. The interaction of polyene antibiotics with thin lipid membranes. J Gen Physiol. 1968 Aug;52(2):300–325. doi: 10.1085/jgp.52.2.300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Blanke T. J., Little J. R., Shirley S. F., Lynch R. G. Augmentation of murine immune responses by amphotericin B. Cell Immunol. 1977 Sep;33(1):180–190. doi: 10.1016/0008-8749(77)90145-9. [DOI] [PubMed] [Google Scholar]
  3. Cass A., Finkelstein A., Krespi V. The ion permeability induced in thin lipid membranes by the polyene antibiotics nystatin and amphotericin B. J Gen Physiol. 1970 Jul;56(1):100–124. doi: 10.1085/jgp.56.1.100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Hait W. N., Stein J. M., Koletsky A. J., Harding M. W., Handschumacher R. E. Activity of cyclosporin A and a non-immunosuppressive cyclosporin against multidrug resistant leukemic cell lines. Cancer Commun. 1989;1(1):35–43. doi: 10.3727/095535489820875462. [DOI] [PubMed] [Google Scholar]
  5. Hamilton K. S., Barber K. R., Davis J. H., Neil K., Grant C. W. Phase behaviour of amphotericin B multilamellar vesicles. Biochim Biophys Acta. 1991 Feb 25;1062(2):220–226. doi: 10.1016/0005-2736(91)90396-p. [DOI] [PubMed] [Google Scholar]
  6. Janoff A. S., Boni L. T., Popescu M. C., Minchey S. R., Cullis P. R., Madden T. D., Taraschi T., Gruner S. M., Shyamsunder E., Tate M. W. Unusual lipid structures selectively reduce the toxicity of amphotericin B. Proc Natl Acad Sci U S A. 1988 Aug;85(16):6122–6126. doi: 10.1073/pnas.85.16.6122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Lopez-Berestein G., Hopfer R. L., Mehta R., Mehta K., Hersh E. M., Juliano R. L. Prophylaxis of Candida albicans infection in neutropenic mice with liposome-encapsulated amphotericin B. Antimicrob Agents Chemother. 1984 Mar;25(3):366–367. doi: 10.1128/aac.25.3.366. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Lopez-Berestein G., Mehta R., Hopfer R. L., Mills K., Kasi L., Mehta K., Fainstein V., Luna M., Hersh E. M., Juliano R. Treatment and prophylaxis of disseminated infection due to Candida albicans in mice with liposome-encapsulated amphotericin B. J Infect Dis. 1983 May;147(5):939–945. doi: 10.1093/infdis/147.5.939. [DOI] [PubMed] [Google Scholar]
  9. Mehta R. T., Mehta K., Lopez-Berestein G., Juliano R. L. Effect of liposomal amphotericin B on murine macrophages and lymphocytes. Infect Immun. 1985 Feb;47(2):429–433. doi: 10.1128/iai.47.2.429-433.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Mehta R., Lopez-Berestein G., Hopfer R., Mills K., Juliano R. L. Liposomal amphotericin B is toxic to fungal cells but not to mammalian cells. Biochim Biophys Acta. 1984 Mar 14;770(2):230–234. doi: 10.1016/0005-2736(84)90135-4. [DOI] [PubMed] [Google Scholar]
  11. Slater L. M., Sweet P., Stupecky M., Gupta S. Cyclosporin A reverses vincristine and daunorubicin resistance in acute lymphatic leukemia in vitro. J Clin Invest. 1986 Apr;77(4):1405–1408. doi: 10.1172/JCI112450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Vecchiarelli A., Verducci G., Perito S., Puccetti P., Marconi P., Bistoni F. Involvement of host macrophages in the immunoadjuvant activity of amphotericin B in a mouse fungal infection model. J Antibiot (Tokyo) 1986 Jun;39(6):846–855. doi: 10.7164/antibiotics.39.846. [DOI] [PubMed] [Google Scholar]

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