Abstract
Similar to the case of insulin-dependent diabetes mellitus (IDDM) in man, diabetes in nonobese diabetic (NOD) mice and that induced by multiple injections of low-dose streptozotocin (SZ) develops in conjunction with insulitis. We have analyzed whether the development of hyperglycemia in low-dose SZ-injected mice can be prevented by administration of the streptococcal preparation, OK-432, which has been reported to inhibit the development of Type 1 diabetes in NOD mice. Eightto ten-week-old male CD-1 mice were given SZ (30 or 40mg/kg body weight) on five consecutive days (day 0-4) and in addition, OK-432 or saline was injected intraperitoneally on days-5, 0, 7 and 14. The mice which received 40mg/kg of SZ became hyperglycemic and the mean blood glucose level was higher in OK-432-injected mice than in saline-injected controls. In the mice receiving 30mg/kg of SZ, 50% of OK-432-injected mice developed hyperglycemia, but saline-injected mice did not develop diabetes within the experimental period. Histological examination showed marked mononuclear cell infiltration of the islets in OK-432-injected mice compared with saline-injected controls. These results suggest that immunomodulators such as OK-432 may, in some cases, enhance islet cell destruction and exacerbate Type 1 diabetes in man.
