Inhibition of adjuvant arthritis in the rat by phosphosugars and the alpha-glucosidase inhibitor castanospermine.
The development of joint inflammation of adoptively transferred arthritis in rats was inhibited by treatment with the simple sugar mannose-6-phosphate or the alkaloid inhibitor of alpha-glucosidase, castanospermine. Mannose-6-phosphate was effective at a dose of 25 mg/kg per day delivered via mini-osmotic pumps implanted either subcutaneously or intraperitoneally. Castanospermine was given orally in the drinking water and rats ingested on average 60-65 mg/kg per day. Histological examination of tissue from treated rats revealed greatly reduced inflammatory infiltrates into the synovium and surrounding tissue. Castanospermine not only inhibited the development of arthritis but also inhibited the progression of the disease when treatment was commenced after the onset of symptoms. Possible mechanism(s) of action of these compounds could be their ability to inhibit the passage of leucocytes through vascular subendothelial basement membranes by inhibiting the function or expression of leucocyte cell surface-bound enzymes that are essential for such migration. Castanospermine could also inhibit inflammation through its ability to prevent the expression of adhesion molecules, which may be necessary for the capture and retention of leucocytes in the inflamed tissue.
Willenborg
D O
DO
Neurosciences Research Unit, Woden Valley Hospital, Canberra, Australia.
Parish
C R
CR
Cowden
W B
WB
D000818:Animals; D001169:Arthritis, Experimental / Q000517:prevention & control*; D065089:Glycoside Hydrolase Inhibitors; D007114:Immunization; D016219:Immunotherapy, Adoptive; D007212:Indolizines / Q000494:pharmacology / Q000627:therapeutic use*; D015918:Infusion Pumps, Implantable; D008297:Male; D008360:Mannosephosphates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D009170:Nontuberculous Mycobacteria / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D054836:Indolizidines
D065089:Glycoside Hydrolase Inhibitors; D007212:Indolizines; D008360:Mannosephosphates; C027693:mannose-6-phosphate; C037806:castanospermine; D054836:Indolizidines