CYTOKINE GENE-EXPRESSION IN ISLETS AND THYROIDS OF BB RATS - IFN-GAMMA AND IL-12P40 MESSENGER-RNA INCREASE WITH AGE IN BOTH DIABETIC AND INSULIN-TREATED NONDIABETIC BB RATS

Inflammatory cytokines, particularly those produced by Th1 type lympho cytes, are hypothesized to play a major role in the pathogenesis of au toimmune diseases. The present studies investigated this hypothesis in the BB rat. Diabetes-prone (DP) BB rats develop spontaneous hyperglyc emia and thyroiditis. Coisogenic diabetes-resistant (DR) BB rats do no t develop either disorder spontaneously, but both diseases are induced by depletion of RT6(+) T cells. Reverse transcriptase-PCR was used to measure mRNA encoding type 1 and type 2 cytokines. In both DP and RT6 -depleted DR rats, IFN-gamma mRNA was present in islets before and dur ing disease onset. IL-2 and IL-4 mRNAs were minimal or undetectable in infiltrated islets but present in activated peripheral T cells. IL-10 mRNA was present at low abundance in infiltrating T cells. These obse rvations suggested a Th1 type inflammatory response, and consistent wi th this interpretation, we observed that mRNA encoding the p40 chain o f IL-12 was also present before and during disease onset. Similar cyto kine mRNA profiles were observed in the thyroids of RT6-depleted DR ra ts and in the islets of DP rats treated with prophylactic parenteral i nsulin to prevent diabetes. We conclude that IFN-gamma and IL-12 may p lay a major role in the expression of insulitis and thyroiditis in the BB rat, that Th1 lymphocytes may predominate over Th2 lymphocytes in these inflammatory lesions, and that prevention of diabetes by insulin is not associated with an alteration in the cytokine gene profile of islet infiltrating cells.