Macrophage depletion by albumin microencapsulated clodronate: Attenuation of cytokine release in macrophage-dependent glomerulonephritis

A macrophage plays an important role in mediating the inflammatory response . Cytokines released by activated macrophages contribute to inflammation in glomerulonephritis (GN). Clodronate, a biphosphonate, causes macrophage de pletion when administered in an encapsulated form in liposomes. We used alb umin as the polymer matrix to microencapsulate clodronate to the microspher es (MS) in the 1-mu m size range. The purpose of this study was to (a) dete rmine macrophage depletion by clodronate MS, (b) determine the effect of cl odronate MS on endotoxin-induced cytokine release in vitro, and (c) assess the effect of clodronate MS on macrophage infiltration ill experimental ant iglomerular basement membrane nephritis. Macrophage depletion by clodronate MS was assessed by staining for the ED1 marker. The results indicate great er than 95% depletion of macrophages from the spleen, liver, kidney, and bl ood in the whole blood model, clodronate MS attenuated endotoxin-induced tu mor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) re lease, and the attenuation by the microencapsulated form of clodronate was also more effective than the free (solution) farm of clodronate. Macrophage infiltration into the glomerulus in experimental GN was also blocked very effectively by pretreatment with clodronate MS. In conclusion, macrophage d epletion by clodronate MS may be beneficial in reducing cytokine release an d renal damage in GN.