Comparative Effects of Amphotericin B (AMB) and its Lipid Formulations on Release of Cytokines and Chemokines from Human Monocytes.

M. SIMITSOPOULOU, J. DOTIS1, A. MALOUKOU, F. DUDKOVA, T.J. WALSH, E. ROILIDES

Author address: 

Aristotle Univ., Thessaloniki, Greece, Atei, Thessaloniki, Greece, NCI, Bethesda, MD.

Abstract: 

Background: Invasive fungal infections are an increasing problem in recent years associated with significant morbidity and mortality. Deoxycholate amphotericin B (DAMB) and AMB lipid formulations such as liposomal (LAMB), lipid complex (ABLC) and colloidal dispersion (ABCD), are commonly used antifungal therapy. We studied the effects of AMB formulations on cytokine/chemokine release from monocytes. Methods: Human monocytes purified by dextran sedimentation and plastic adherence were incubated with AMB formulations for 2-24 h. Culture supernatants and cell extracts were then collected. Interleukin-1b (IL-1b), IL-1 receptor antagonist (IL-1ra), tumor necrosis factor-a (TNF-a), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1b (MIP-1b) were measured by ELISA. Friedman and Dunn's tests were used. Results: Cytokine IL-1b IL-1ra TNF-a MCP-1 MIP-1b (pg/ml) (n=7) (n=7) (n=5) (n=8) (n=6) Monocytes 256±45 1433±400 7.3±1.8 378±95 5847±1220 Drug concentration (mg/l) DAMB-1 383±45 1011±230** 6.9±2.5 521±53 7050±783 DAMB-5 1219±212** 936±206* 4.8±1.1 538±210 8587±1892 LAMB-5 202±25 818±148* 4.2±1.0 392±80 5331±1281 LAMB-25 225±32 777±142** 3.9±1.1 363±130 4813±1647 ABCD-5 339±45 1113±327 7.4±0.9 471±64* 8613±2151* ABCD-25 423±71* 1111±274 7.9±1.9 383±58 7278±1887 ABLC-5 170±46* 1157±363 6.5±2.2 242±27 3036±986 ABLC-25 306±62 905±231** 3.4±1.1* 261±82* 3021±1269 Data are mean±SEM, n=5-8, *p
2003

abstract No: 

M-1247

Full conference title: 

43rd Interscience Conference on Antimicrobial Agents
    • ICAAC 43rd