Immunomodulatory effects of three macrolides, midecamycin acetate, josamycin, and clarithromycin, on human T-lymphocyte function in vitro.
The effect of three macrolide antibiotics, midecamycin acetate, josamycin, and clarithromycin, on human T-cell function was investigated in vitro. Midecamycin acetate and josamycin suppressed the proliferative response of peripheral blood mononuclear cells stimulated by polyclonal T-cell mitogens at concentrations between 1.6 and 8 micrograms/ml. At higher concentrations (40 to 200 micrograms/ml), all these drugs showed a marked inhibitory effect. At concentrations of 1.6 to 40 micrograms/ml, these drugs suppressed interleukin-2 (IL-2) production induced by mitogen-stimulated T cells, but not the expression of IL-2 receptor (CD25), in a dose-dependent manner. Therefore, the suppressive action on T-lymphocyte proliferation seems to be based on the ability of these drugs to inhibit IL-2 production by T cells. The drug also inhibited mixed lymphocyte reaction at the same concentrations. Combined treatment with these macrolides and the known immunosuppressants such as FK506 and cyclosporin A resulted in an increased inhibition of T-cell proliferation. The immunomodulatory properties of the antibiotics may have clinical relevance for modulation of the immune response in transplant patients and in patients with inflammatory diseases.
Morikawa
K
K
Department of Internal Medicine, Shimane Medical University, Japan.
Oseko
F
F
Morikawa
S
S
Iwamoto
K
K
D000276:Adjuvants, Immunologic / Q000097:blood / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000097:blood / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D017291:Clarithromycin / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D015570:Josamycin / Q000494:pharmacology; D007700:Kinetics; D007933:Leucomycins / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D015375:Receptors, Interleukin-2 / Q000187:drug effects; D013268:Stimulation, Chemical; D013601:T-Lymphocytes / Q000187:drug effects*; D016559:Tacrolimus / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D000900:Anti-Bacterial Agents; D007376:Interleukin-2; D007933:Leucomycins; D015375:Receptors, Interleukin-2; D016572:Cyclosporine; D017291:Clarithromycin; D015570:Josamycin; C026483:midecamycin; D016559:Tacrolimus