Cytokine Gene Expression in Pancreatic Islet-Infiltrating Leukocytes of BB Rats: Expression of Th1 Cytokines Correlates With β-Cell Destructive Insulitis and IDDM

Cytokines produced by islet-infiltrating mononuclear leukocytes may be involved in islet β-cell destruction and IDDM. To determine which cytokine(s) might be involved in islet β-cell destruction, we used a reverse transcriptase–polymerase chain reaction assay to compare levels of cytokine mRNA expression in mononuclear leukocytes freshly isolated from islets of four groups of BB rats aged 60–75 days: diabetes-prone (DP) rats, DP rats protected from diabetes by injection of complete Freund's adjuvant (CFA) at age 25 days, acutely diabetic rats, and diabetes-resistant (DR) rats. We found that islet mononuclear leukocyte levels of γ-interferon (IFN-γ) mRNA were significantly higher in DP and diabetic rats than in DR rats, whereas CFA-treated DP rats had similar IFN-γ mRNA levels to DR rats. Also, interleukin (IL)-2 mRNA levels tended to be higher in islet leukocytes from DP and diabetic rats than from DR rats. Tumor necrosis factor-ɑ, IL-4, and IL-10 mRNA levels were not significantly different in islet leukocytes from the four groups of rats. These findings suggest that production of T-helper 1 (Th1)-type cytokines, IFN-γ and IL-2, by islet-infiltrating cells in BB rats is associated with β-cell destruction and IDDM development.