INTERLEUKIN-1-BETA INHIBITS RAT-THYROID CELL-FUNCTION IN-VIVO AND IN-VITRO BY AN NO-INDEPENDENT MECHANISM AND INDUCES HYPOTHYROIDISM AND ACCELERATED THYROIDITIS IN DIABETES-PRONE BB RATS

Interleukin-1 beta has been implicated as a pathogenic factor in the d evelopment of autoimmune thyroiditis. When given for 5 days to normal non-diabetes-prone Wistar Kyoto rats, it decreased plasma concentratio ns of total tri-iodothyronine and thyroxine and increased plasma TSH. These effects were not prevented by co-injection of nitroarginine meth yl ester or aminoguanidine, inhibitors of NO synthases. Exposure to in terleukin-1 beta dose-dependently reduced iodine uptake in FRTL-5 cell s, but had no effect on thyroglobulin secretion. Nitrite was not detec ted in the FRTL-5 cell culture media after exposure to interleukin-1 b eta. However, reverse transcription PGR analysis of mRNA isolated from interleukin-1 beta-exposed FRTL-5 cells revealed a transitory express ion of the inducible NO synthase, which was markedly lower than induci ble NO synthase induction in interleukin-1 beta-exposed isolated rat i slets of Langerhans. Go-incubation with the NO synthase inhibitor N-G- monomethylarginine did not ameliorate the effect of interleukin-1 beta on FRTL-5 cell; iodine uptake. Furthermore, we demonstrate that daily injections of interleukin-1 beta for 13 weeks aggravated spontaneous thyroiditis and induced severe hypothyroidism in non-diabetic diabetes -prone BE rats. The data suggest that NO does not mediate interleukin- 1 beta-induced inhibition of rat thyroid function in vivo or in vitro in FRTL-5 cells, and the induction of hypothyroidism by interleukin-1 beta in diabetes-prone BE rats is speculated to be due to exacerbation of recruitment and activation of intrathyroidal mononuclear cells.