Neutralization of TNF does not influence endotoxin-induced changes in thyroid hormone metabolism in humans

To determine the role of tumor necrosis factor (TNF) in endotoxin-induced c hanges in plasma thyroid hormone and thyroid-stimulating hormone (TSH) conc entrations, 24 healthy postabsorptive humans were studied on a control stud y day (n = 6), after infusion of a recombinant TNF receptor IgG fusion prot ein (TNFR:Fc; 6 mg/m(2); n = 6) after intravenous injection of endotoxin (2 ng/kg; n = 6), or after administration of endotoxin with TNFR:Fc (n = 6). Administration of TNFR:Fc alone did not affect thyroid hormone or TSH level s when compared with the control day. Endotoxin induced a transient rise in plasma TNF activity (1.5 h: 219 +/- 42 pg/ml), which was completely preven ted by TNFR:Fc (P < 0.05). After endotoxin administration, plasma L-thyroxi ne (T-4), free T-4, 3,5,3'-triiodothyronine (T-3), and TSH were lower and 3 ,3',5'-triiodothyronine was higher than on the control day tall P < 0.05). Coinfusion of TNFR:Fc with endotoxin did not influence these endotoxin-indu ced changes. Our results suggest that endogenous TNF does not play an impor tant role in the alterations in plasma thyroid hormone and TSH concentratio ns induced by mild endotoxemia in healthy humans.