EFFECTS OF THE ANTIINFLAMMATORY COMPOUNDS CASTANOSPERMINE, MANNOSE-6-PHOSPHATE AND FUCOIDAN ON ALLOGRAFT-REJECTION AND ELICITED PERITONEAL EXUDATES

The glycoprotein processing inhibitor castanospermine (CS) and the mon osaccharide mannose-6-phosphate (M6P), as well as some sulfated polysa ccharides (SPS), have been shown to inhibit inflammation in rat models of experimental autoimmune encephalomyelitis and adjuvant-induced art hritis. Here, the anti-inflammatory effects of these agents have been further explored in murine models of allograft rejection and elicitati on of peritoneal exudates. CS, M6P and the SPS, fucoidan, partially in hibited rejection of permanently accepted thyroid allografts induced b y the i.p. injection of donor strain (H-2(d)) spleen cells with a redu ction in leucocyte infiltration of 25-36%. However none of these agent s reduced the more extensive leucocyte infiltration induced by the i.p . injection of P815 (H-2(d)) unless recipient mice were pretreated wit h the immunosuppressant, cyclosporin A (CsA). Elicitation of peritonea l exudates by thioglycollate was inhibited by CS, M6P and fucoidan wit h sustained leucopenia being induced by CS. In contrast, CS and fucoid an, but not M6P, inhibited antigen-elicited peritoneal exudates. These results suggest that CS, M6P and the SPS fucoidan exhibit subtle diff erences in their anti-inflammatory activity but probably inhibit infla mmation at the level of leucocyte extravasation.