Immunosuppressive activity of fosfomycin on human T-lymphocyte function in vitro.
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.
Morikawa
K
K
Department of Internal Medicine, Shimane Medical University, Japan.
Oseko
F
F
Morikawa
S
S
Sawada
M
M
D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D004357:Drug Synergism; D005578:Fosfomycin / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects; D010835:Phytohemagglutinins / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000502:physiology; D011990:Receptors, Transferrin; D012756:Sheep; D013268:Stimulation, Chemical; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000502:physiology*; D016559:Tacrolimus / Q000494:pharmacology
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C068126:CD71 antigen; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D010835:Phytohemagglutinins; D015375:Receptors, Interleukin-2; D011990:Receptors, Transferrin; D003208:Concanavalin A; D005578:Fosfomycin; D016572:Cyclosporine; D016559:Tacrolimus