CYTOKINE GENE-EXPRESSION IN PANCREATIC ISLET-INFILTRATING LEUKOCYTES OF BB RATS - EXPRESSION OF TH1 CYTOKINES CORRELATES WITH BETA-CELL DESTRUCTIVE INSULITIS AND IDDM

Cytokines produced by islet-infiltrating mononuclear leukocytes may be involved in islet beta-cell destruction and IDDM. To determine which cytokine(s) might be involved in islet beta-cen destruction, we used a reverse transcriptase-polymerase chain reaction assay to compare leve ls of cytokine mRNA expression in mononuclear leukocytes freshly isola ted from islets of four groups of BE rats aged 60-75 days: diabetes-pr one (DP) rats, DP rats protected from diabetes by injection of complet e Freund's adjuvant (CFA) at age 25 days, acutely diabetic rats, and d iabetes-resistant (DR) rats, We found that islet mononuclear leukocyte levels of gamma-interferon (IFN-gamma) mRNA were significantly higher in DP and diabetic rats than in DR rats, whereas CFA-treated DP rats had similar IFN-gamma mRNA levels to DR rats, Also, interleukin (IL)-2 mRNA levels tended to be higher in islet leukocytes from DP and diabe tic rats than from DR rats, Tumor necrosis factor-alpha, IL-4, and IL- 10 mRNA levels were not significantly different in islet leukocytes fr om the four groups of rats, These findings suggest that production of T-helper 1 (Th1)-type cytokines, IFN-gamma and IL-2, by islet-infiltra ting cells in BE rats is associated with beta-cen destruction and IDDM development.