Chronic infusion of TNF-alpha reduces plasma T4 binding without affecting pituitary-thyroid activity in rats

In the present study the effects of continuous administration of tumor necrosis factor-alpha (TNF-alpha), in a dose not affecting body temperature and food intake, on pituitary-thyroid function of rats were investigated. Male rats, bearing a venous catheter to allow repeated blood sampling, were intraperitoneally equipped with osmotic minipumps that continuously delivered recombinant human TNF-alpha (8.0 micrograms/day ip) or saline for 7 days. Infusion of TNF-alpha resulted in a significant decrease of plasma total thyroxine (T4) levels during days 2-5 of infusion as compared with the levels in saline-infused rats. This suppression of plasma T4 concentrations was caused by a decreased binding of T4 in plasma, as indicated by an increased percentage of free T4. TNF-alpha infusion did not significantly affect free T4 levels in plasma nor basal and thyrotropin-releasing hormone-stimulated TSH levels. The decreased binding of T4 was, at least partially, caused by a reduction of T4-binding prealbumin (TBPA) levels in plasma, which were significantly reduced during the first 3 days of TNF-alpha infusion. Plasma levels of free fatty acids were not affected by TNF-alpha. TNF-alpha treatment did not influence the plasma 3,5,3'-triiodothyronine (T3)-to-T4 ratio nor hepatic 5'-deiodinase activity. Plasma reverse T3 levels remained undetectable both in control and TNF-alpha-treated rats. Taken together, our findings indicate that chronic infusion of rats with TNF-alpha in a subpyrogenic and subanorectic dose induces a transient decrease of plasma T4 binding without affecting pituitary-thyroid activity and peripheral thyroid hormone metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)