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Am J Physiol Regul Integr Comp Physiol 276: R357-R362, 1999;
0363-6119/99 $5.00
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Vol. 276, Issue 2, R357-R362, February 1999

Neutralization of TNF does not influence endotoxininduced changes in thyroid hormone metabolism in humans

Tom van der Poll1,2, Erik Endert3, Susette M. Coyle1, Jan M. Agosti4, and Stephen F. Lowry1

1 Division of Surgical Sciences, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey 08903; 2 Department of Internal Medicine and 3 Laboratory of Endocrinology, Academic Medical Center, University of Amsterdam, Amsterdam 1105AZ, The Netherlands; and 4 Immunex Company, Seattle, Washington 98101

To determine the role of tumor necrosis factor (TNF) in endotoxin-induced changes in plasma thyroid hormone and thyroid-stimulating hormone (TSH) concentrations, 24 healthy postabsorptive humans were studied on a control study day (n = 6), after infusion of a recombinant TNF receptor IgG fusion protein (TNFR:Fc; 6 mg/m2; 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 levels 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 prevented by TNFR:Fc (P < 0.05). After endotoxin administration, plasma L-thyroxine (T4), free T4, 3,5,3'-triiodothyronine (T3), and TSH were lower and 3,3',5'-triiodothyronine was higher than on the control day (all P < 0.05). Coinfusion of TNFR:Fc with endotoxin did not influence these endotoxin-induced changes. Our results suggest that endogenous TNF does not play an important role in the alterations in plasma thyroid hormone and TSH concentrations induced by mild endotoxemia in healthy humans.

lipopolysaccharide; cytokines; thyrotropin


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