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

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.

[1]  J. Hershman,et al.  Tumor Necrosis Factor, Ceramide, Transforming Growth Factor-β1, and Aging Reduce Na+/I- Symporter Messenger Ribonucleic Acid Levels in FRTL-5 Cells. , 1998, Endocrinology.

[2]  J. Hershman,et al.  Sphingomyelinase and phospholipase A2 regulate type I deiodinase expression in FRTL-5 cells. , 1997, Thyroid : official journal of the American Thyroid Association.

[3]  T. van der Poll,et al.  Effect of a recombinant dimeric tumor necrosis factor receptor on inflammatory responses to intravenous endotoxin in normal humans. , 1997, Blood.

[4]  J. Hershman,et al.  Tumor Necrosis Factor-α (TNF-α) and Transforming Growth Factor-βl (TGF-βl) Inhibit the Expression and Activity of Na+/K+-ATPase in FRTL-5 Rat Thyroid Cells , 1997 .

[5]  T. van der Poll,et al.  Down-regulation of surface receptors for TNF and IL-1 on circulating monocytes and granulocytes during human endotoxemia: effect of neutralization of endotoxin-induced TNF activity by infusion of a recombinant dimeric TNF receptor. , 1997, Journal of immunology.

[6]  W. Wiersinga,et al.  Induced illness in interleukin-6 (IL-6) knock-out mice: a causal role of IL-6 in the development of the low 3,5,3'-triiodothyronine syndrome. , 1996, Endocrinology.

[7]  W. Wiersinga,et al.  Thyroid hormone metabolism in nonthyroidal illness , 1996 .

[8]  C. Dinarello,et al.  Biologic basis for interleukin-1 in disease. , 1996, Blood.

[9]  S. Banks,et al.  Effects of recombinant dimeric TNF receptor on human inflammatory responses following intravenous endotoxin administration. , 1995, Journal of immunology.

[10]  J. Romijn,et al.  Acute effects of interferon-alpha administration on thyroid hormone metabolism in healthy men. , 1995, The Journal of clinical endocrinology and metabolism.

[11]  S. Lowry,et al.  Biological Responses to Endotoxin in Humans1 , 1995 .

[12]  T. van der Poll,et al.  Interleukin-1 receptor blockade does not affect endotoxin-induced changes in plasma thyroid hormone and thyrotropin concentrations in man. , 1995, The Journal of clinical endocrinology and metabolism.

[13]  L. Braverman,et al.  Tumor necrosis factor-alpha and interferon-gamma modulate gene expression of type I 5'-deiodinase, thyroid peroxidase, and thyroglobulin in FRTL-5 rat thyroid cells. , 1995, Endocrinology.

[14]  H. Loetscher,et al.  Protective effect of 55- but not 75-kD soluble tumor necrosis factor receptor-immunoglobulin G fusion proteins in an animal model of gram- negative sepsis , 1994, The Journal of experimental medicine.

[15]  K. Bendtzen,et al.  Influence of tumour necrosis factor-alpha, tumour necrosis factor-beta and interferon-gamma, separately and added together with interleukin-1 beta, on the function of cultured human thyroid cells. , 1994, The Journal of endocrinology.

[16]  T. van der Poll,et al.  Effects of acute and chronic interleukin-6 administration on thyroid hormone metabolism in humans. , 1994, The Journal of clinical endocrinology and metabolism.

[17]  F. Santini,et al.  Cytokines modulate type I iodothyronine deiodinase mRNA levels and enzyme activity in FRTL-5 rat thyroid cells , 1994, Molecular and Cellular Endocrinology.

[18]  L. Braverman,et al.  Tumor necrosis factor-alpha decreases thyrotropin-induced 5'-deiodinase activity in FRTL-5 thyroid cells. , 1994, European journal of endocrinology.

[19]  T. van der Poll,et al.  Differential effects of anti-tumor necrosis factor monoclonal antibodies on systemic inflammatory responses in experimental endotoxemia in chimpanzees. , 1994, Blood.

[20]  C A Smith,et al.  Soluble tumor necrosis factor (TNF) receptors are effective therapeutic agents in lethal endotoxemia and function simultaneously as both TNF carriers and TNF antagonists. , 1993, Journal of immunology.

[21]  T. van der Poll,et al.  Tumor necrosis factor: a putative mediator of the sick euthyroid syndrome in man. , 1990, The Journal of clinical endocrinology and metabolism.

[22]  M. Sugawara,et al.  The mechanism of action of tumour necrosis factor-alpha and interleukin 1 on FRTL-5 rat thyroid cells. , 1990, Acta endocrinologica.

[23]  Kanji Sato,et al.  Inhibition of 125I Organification and Thyroid Hormone Release by Interleukin-1, Tumor Necrosis Factor-α, and Interferon-γ in Human Thyrocytes in Suspension Culture* , 1990 .

[24]  J. Hershman,et al.  Characterization of tumor necrosis factor-alpha receptors in human and rat thyroid cells and regulation of the receptors by thyrotropin. , 1989, Endocrinology.

[25]  I. Todd,et al.  Influence of Tumor Necrosis Factor-α on the Modulation by Interferon-γ of HLA Class II Molecules in Human Thyroid Cells and Its Effect on Interferon-γ Binding , 1989 .

[26]  J. Hershman,et al.  Impairment of hypothalamic-pituitary-thyroid function in rats treated with human recombinant tumor necrosis factor-alpha (cachectin). , 1989, Endocrinology.

[27]  M. Kawakami,et al.  Effects of Tumor Necrosis Factor-α/Cachectin on Thyroid Hormone Metabolism in Mice , 1988 .

[28]  Kevin J. Tracey,et al.  Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia , 1987, Nature.

[29]  R. I. Gregerman,et al.  Suppression of thyrotropin in the low-thyroxine state of severe nonthyroidal illness. , 1985, The New England journal of medicine.

[30]  K. Burman,et al.  Alterations in thyroid function in patients with systemic illness: the "euthyroid sick syndrome". , 1982, Endocrine reviews.

[31]  T. van der Poll,et al.  Tumor necrosis factor in sepsis: mediator of multiple organ failure or essential part of host defense? , 1995, Shock.

[32]  J. Hershman,et al.  Action of tumor necrosis factor-alpha on thyroid cells. , 1994, Transactions of the American Clinical and Climatological Association.

[33]  J. Hershman,et al.  Suppression of rat thyrotroph and thyroid cell function by tumor necrosis factor-alpha. , 1993, Thyroid : official journal of the American Thyroid Association.

[34]  J. Lamb,et al.  Detection of in vivo production of tumour necrosis factor-alpha by human thyroid epithelial cells. , 1992, Immunology.

[35]  W. Wiersinga,et al.  Decreased nocturnal surge of thyrotropin in nonthyroidal illness. , 1990, The Journal of clinical endocrinology and metabolism.

[36]  W. Wiersinga,et al.  Radioimmunoassay of thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (reverse T3, rT3), and 3,3'-diiodothyronine (T2). , 1982, Methods in enzymology.