Skip to main content
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1993 Dec;37(12):2684–2687. doi: 10.1128/aac.37.12.2684

Immunosuppressive activity of fosfomycin on human T-lymphocyte function in vitro.

K Morikawa 1, F Oseko 1, S Morikawa 1, M Sawada 1
PMCID: PMC192778  PMID: 7509146

Abstract

Recent investigations have shown that some antibiotics also work as immunomodulators. We have recently reported that fosfomycin (FOM) has an immunomodulatory effect on human B-cell activation. FOM is a unique antibiotic which is chemically unrelated to any other known antibacterial agent. In the present study, we examined the effect of FOM on human T-cell function. FOM inhibited the proliferation of human lymphocytes induced by polyclonal T-cell mitogens in a dose-dependent manner. FOM also strongly suppressed mixed lymphocyte reaction and interleukin-2 (IL-2) production by T cells. Moreover, FOM inhibited the expressions of IL-2 receptor (CD25) and transferrin receptor (CD71) on the activated T-cell surfaces. These data suggest that FOM may block the T-cell division during the transition from G1 to S phase of the cell cycle. Combined treatment with FOM and low-dose cyclosporin A or FK506 caused additive or synergistic suppression of T-cell proliferation, but not on IL-2 receptor expression. It seems that the mode of action of FOM on T-cell function involves a specific suppression of IL-2 production.

Full text

PDF
2685

Selected References

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

  1. Bunjes D., Hardt C., Röllinghoff M., Wagner H. Cyclosporin A mediates immunosuppression of primary cytotoxic T cell responses by impairing the release of interleukin 1 and interleukin 2. Eur J Immunol. 1981 Aug;11(8):657–661. doi: 10.1002/eji.1830110812. [DOI] [PubMed] [Google Scholar]
  2. Häyry P., Andersson L. C., Nordling S., Virolainen M. Allograft response in vitro. Transplant Rev. 1972;12:91–140. doi: 10.1111/j.1600-065x.1972.tb00054.x. [DOI] [PubMed] [Google Scholar]
  3. Kahan F. M., Kahan J. S., Cassidy P. J., Kropp H. The mechanism of action of fosfomycin (phosphonomycin). Ann N Y Acad Sci. 1974 May 10;235(0):364–386. doi: 10.1111/j.1749-6632.1974.tb43277.x. [DOI] [PubMed] [Google Scholar]
  4. Larsson E. L. Cyclosporin A and dexamethasone suppress T cell responses by selectively acting at distinct sites of the triggering process. J Immunol. 1980 Jun;124(6):2828–2833. [PubMed] [Google Scholar]
  5. Morikawa K., Morikawa S., Imai K., Oseko F. Regulation of lymphocyte blastogenesis and antibody production by soluble factor released by a human B-lymphoblastoid cell line. Cytokine. 1991 Nov;3(6):609–610. doi: 10.1016/1043-4666(91)90488-y. [DOI] [PubMed] [Google Scholar]
  6. Morikawa K., Oseko F., Morikawa S. Immunomodulatory effect of fosfomycin on human B-lymphocyte function. Antimicrob Agents Chemother. 1993 Feb;37(2):270–275. doi: 10.1128/aac.37.2.270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Neckers L. M., Cossman J. Transferrin receptor induction in mitogen-stimulated human T lymphocytes is required for DNA synthesis and cell division and is regulated by interleukin 2. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3494–3498. doi: 10.1073/pnas.80.11.3494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Takeshita K., Yamagishi I., Harada M., Otomo S., Nakagawa T., Mizushima Y. Immunological and anti-inflammatory effects of clarithromycin: inhibition of interleukin 1 production of murine peritoneal macrophages. Drugs Exp Clin Res. 1989;15(11-12):527–533. [PubMed] [Google Scholar]
  9. Thomson A. W. FK-506--how much potential? Immunol Today. 1989 Jan;10(1):6–9. doi: 10.1016/0167-5699(89)90057-1. [DOI] [PubMed] [Google Scholar]
  10. Thomson A. W., Moon D. K., Geczy C. L., Nelson D. S. Cyclosporin A inhibits lymphokine production but not the responses of macrophages to lymphokines. Immunology. 1983 Feb;48(2):291–299. [PMC free article] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES