Antilymphocytic activity of erythromycin distinct from that of FK506 or cyclosporin A

J Antibiot (Tokyo). 1993 Sep;46(9):1406-13. doi: 10.7164/antibiotics.46.1406.


Erythromycin (EM), a macrolide antibiotic has been recently reported to depress the extent of inflammation irrespective of its antimicrobial action. Our study was initiated to examine the effect of EM on T cell proliferation in vitro, since other macrolide antibiotics FK506 and rapamycin (RAP) have been well known to possess strong immunosuppressive or anti-inflammatory potential. EM had a suppressive effect on the proliferative response of human lymphocytes stimulated with mitogens and antigens, while EM had no effect on concanavalin A (Con A)-induced interleukin-2 (IL-2) production or IL-2R alpha (CD25) expression. Delayed addition of EM after the first 48 hours of mitogenic stimulation did suppress IL-2-dependent proliferation of Con A blasts, whereas pretreatment with EM for the first 48 hours of stimulation did not impede the subsequent IL-2-dependent proliferation of obtained blast cells. The results indicate that EM suppresses T cell proliferation at a late stage in the activation process by impairing their response to IL-2. This antilymphocytic action of EM was quite distinct from that of FK506 or cyclosporin A (CsA) but was similar to that of RAP. Unlike RAP, however, EM did not antagonize FK506-induced suppression but potentiated the action of FK506 and CsA. The addition of an enteric hormone motilin, a receptor of which was previously found to be occupied by EM, unaffected the lymphocyte proliferation and the subsequent EM-induced suppression. These data suggest that EM operates through an undefined mechanism probably distinct from that of FK506, CsA, RAP or motilin.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens / immunology
  • Cell Line
  • Concanavalin A / pharmacology
  • Cyclosporine / pharmacology*
  • Drug Synergism
  • Erythromycin / pharmacology*
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • Interleukin-2 / biosynthesis
  • Lymphocyte Activation
  • Lymphocytes / drug effects*
  • Lymphocytes / immunology
  • Lymphocytes / metabolism
  • Motilin / pharmacology
  • Receptors, Interleukin-2 / metabolism
  • Tacrolimus / pharmacology*
  • Tumor Cells, Cultured


  • Antigens
  • Immunosuppressive Agents
  • Interleukin-2
  • Receptors, Interleukin-2
  • Concanavalin A
  • Motilin
  • Erythromycin
  • Cyclosporine
  • Tacrolimus