EFFECT OF MACROPHAGE DEPLETION BY LIPOSOMES CONTAINING DICHLOROMETHYLENE-DIPHOSPHONATE ON ENDOTOXIN-INDUCED UVEITIS

Footpad injection of lipopolysaccharide (LPS) from Salmonella typhimur ium in Lewis rats induces an acute anterior and posterior endotoxin-in duced uveitis (EIU). To investigate the role of macrophages in the pat hogenesis of EIU, we eliminated macrophages by means of liposomes cont aining dichloromethylene-diphosphonate (Cl2MDP), a drug which depletes macrophages but not other immunocompetent cells. Intravenous injectio n of CL2MDP-liposomes clearly inhibited clinical and histological mani festations of uveitis in the anterior segment of the eye (iris/ciliary body) and reduced TNF level in aqueous humor. Specific immunostaining showed that CL2MDP-liposome injections decreased the number of ED2 resident macrophages in the iris/ciliary body and the choroid. After L PS injection, CL2MDP-liposome treatment reduced the density of infiltr ating ED1 + cells (mainly monocytes / macrophages) in the iris/ciliary body but not in the choroid; little or no effect was detected on the OX42 + cellular infiltration (mainly polymorphonuclear leukocytes). Th e inflammatory cellular infiltration of the retina was not modified by the treatment. These findings suggest that macrophages play a key rol e in the pathogenesis of ocular inflammation. (C) 1998 Elsevier Scienc e B.V. All rights reserved.