Immunomodulatory effects of amphotericin-B on cellular cytotoxicity of normal human lymphocytes

Abstract

Human peripheral blood lymphocytes (PBL) precultured in media demonstrated decreased NK and ADCC activities as an apparent consequence of endogenous suppressor cells generated in the culture. PBL precultured with amphotericin-B (AMB) for 48 hr showed further decreases of NK and ADCC activities. T cells, Sephadex G-10 column passed PBL, and NK-and ADCC-enriched subpopulations separated on a Percoll gradient precultured with AMB also manifested decreased NK and ADCC activities. In mixing experiments, lymphocytes precultured with AMB suppressed the ADCC activities of fresh autologous effector cells. The suppression of ADCC activities observed was not due to crowding, selective toxicity, steric hindrance, effector or target cell death from AMB or desoxycholate, or the presence of PBL causing cold target competitive inhibition or binding. AMB-enhanced suppression was not reversed by indomethacin. The results suggest that AMB has a significant immunomodulating effect on human PBL possibly by activating endogenous suppressor cells which may be of clinical significance.