Immunomodulatory effects of erythromycin and its derivatives on human T-lymphocyte in vitro.

To elucidate the immunomodulatory mechanisms of macrolides, we investigated here the effects of erythromycin (EM) and its derivatives, 1 and 2, which show no antibacterial activity, on the proliferation and the activation of the transcription factor nuclear factor-kappaB (NF-kappaB) in Jurkat T cells. MTT assay revealed that EM, 1 and 2 could inhibit T lymphocyte proliferation markedly. Flow cytometry and TUNEL analysis showed EM (30 microg/mL-100 microg/mL) and 1 (3 microg/mL-30 microg/mL) could induce T lymphocyte apoptosis, 2 (3 microg/mL-30 microg/mL) induced a cell cycle arrest in G(2)/M. RT-PCR and Western blotting analysis conformed that EM and its two derivatives could inhibit the expressions of NF-kappaB mRNA and protein. Taken together, these data suggest EM and its derivatives, 1 and 2, have immunomodulatory effect, presumably via an interaction with the NF-kappaB expression, inhibiting the proliferation of T lymphocyte, implicating an approach for the development of new drugs for treating inflammatory diseases.