THE EFFECT OF FREE GALLIUM AND GALLIUM IN LIPOSOMES ON CYTOKINE AND NITRIC-OXIDE SECRETION FROM MACROPHAGE-LIKE CELLS IN-VITRO

The aim of this study was to evaluate the effect of gallium nitrate, g allium-nitrilotriacetate (NTA) complex, and liposomal gallium-NTA on I L-6, TNF alpha, and nitric oxide (NO) release from activated macrophag es. In addition, the expression of the inducible nitric oxide synthase (iNOS) was determined. Gallium inhibited dose-dependently the secreti on of IL-6, TNF alpha, and NO from the LPS-induced macrophage-like RAW 264 cells. Encapsulation of gallium in negatively charged DSPG-liposo mes increased its potency 10-50 times and 7-11 times compared to free gallium nitrate and gallium-NTA, respectively. Neither non-loaded lipo somes nor NTA alone inhibited cytokine or NO secretion, demonstrating that the observed effects originated from gallium. Liposomal gallium-N TA inhibited the expression of iNOS by the macrophages, while other fo rmulations of gallium had no effect. Thus, gallium, when delivered pro perly, suppresses macrophage functions by inhibiting the release of in flammatory mediators from the cells.