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 development of autoimmune thyroiditis. When given for 5 days to normal non-diabetes-prone Wistar Kyoto rats, it decreased plasma concentrations of total tri-iodothyronine and thyroxine and increased plasma TSH. These effects were not prevented by co-injection of nitroarginine methyl ester or aminoguanidine, inhibitors of NO synthases. Exposure to interleukin-1 beta dose-dependently reduced iodine uptake in FRTL-5 cells, but had no effect on thyroglobulin secretion. Nitrite was not detected in the FRTL-5 cell culture media after exposure to interleukin-1 beta. However, reverse transcription PCR analysis of mRNA isolated from interleukin-1 beta-exposed FRTL-5 cells revealed a transitory expression of the inducible NO synthase, which was markedly lower than inducible NO synthase induction in interleukin-1 beta-exposed isolated rat islets of Langerhans. Co-incubation with the NO synthase inhibitor NG-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 BB 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 BB rats is speculated to be due to exacerbation of recruitment and activation of intrathyroidal mononuclear cells.
Reimers
J I
JI
Steno Diabetes Center, Gentofte, Denmark.
Rasmussen
A K
AK
Karlsen
A E
AE
Bjerre
U
U
Liang
H
H
Morin
O
O
Andersen
H U
HU
Mandrup-Poulsen
T
T
Burger
A G
AG
Feldt-Rasmussen
U
U
Nerup
J
J
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D003920:Diabetes Mellitus; D007037:Hypothyroidism / Q000139:chemically induced*; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011910:Rats, Brattleboro; D011921:Rats, Inbred WKY; D011994:Recombinant Proteins / Q000494:pharmacology; D013961:Thyroid Gland / Q000187:drug effects*; D013966:Thyroiditis / Q000139:chemically induced*
D007375:Interleukin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase