Abstract
Cytokines are thought to be involved in the pathogenesis the euthyroid sick syndrome. Experimental data from in vitro and animal in vivo studies suggest that interferon-γ (IFN-γ) could be another cytokine that might influence thyroid hormone metabolism, although in a previous study in healthy subjects we could not demonstrate an effect of IFN-γ on thyroid hormone indices. Possibly, however, a non-stressed system is not a representative environment to study the effects of a mediator, which might exert its role during pathological circumstances in which it may interact synergistically with other inflammatory mediators. Therefore, we studied the effects of a single dose of recombinant human IFN-γ (Immukine, 100 μg/m2, sc) on thyroid hormone concentrations in a placebo-controlled trial in 13 major surgery patients. Basal IFN-γ levels did not increase. IFN-γ induced a significant increase in monocyte HLA-DR expression (post-operative 50%; 24 h after IFN-γ 90%), but did not affect thyroid hormone and thyroid stimulating hormone concentrations. We therefore conclude that IFN-γ does not appear to be involved in the major changes in thyroid hormone metabolism in patients with non-thyroidal illness.
Similar content being viewed by others
References
Wartofsky L, Burman K.D. Alterations in thyroid function in patients with systemic illness: the “euthyroid sick syndrome”. Endocr. Rev. 1982, 3: 164–217.
Kaptein E.M. Thyroid hormone metabolism in illness: In: Henneman G. (Ed.), Thyroid hormone metabolism. Dekker M., New York, 1986, p. 297.
Wehmann R.E., Gregerman R.I., Burns W.H., Saral R., Santos G.W. Suppression of thyrotropin in the low-thyroxine state of severe nonthyroidal illness. N. Engl. J. Med. 1985, 312: 546–552.
Romijn J.A., Sauerwein H.P. Role of cytokines in thyroid functions: In: Aggarwal B.B., Puti R.K. (Eds.), Human cytokines: their role in disease and therapy. Blackwell Science, Massachusetts, 1995, p. 315.
Bartalena L., Bogazzi F., Brogioni S., Grasso L., Martino E. Role of cytokines in the pathogenesis of the euthyroid sick syndrome. Eur. J. Endocrinol. 1998, 138: 603–614.
Zakarija M., McKenzie J.M. Influence of cytokines on growth and differentiated function of FRTL5 cells. Endocrinology 1989, 125: 1260–1265.
Boelen A., Maas M.A., Lowik C.W., Platvoet M.C., Wiersinga W.M. 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. Endocrinology 1996, 137: 5250–5254.
Boelen A., Platvoet-ter Schiphorst M.C., Wiersinga W.M. Association between serum interleukin-6 and serum 3,5,3’- triiodothyronine in nonthyroidal illness. J. Clin. Endocrinol. Metab. 1993, 77: 1695–1699.
Van der Poll T., Romijn J.A., Wiersinga W.M., Sauerwein H.P. Tumor necrosis factor: a putative mediator of the sick euthyroid syndrome in man. J. Clin. Endocrinol. Metab. 1990, 71: 1567–1572.
Stouthard J.M., Van der Poll T., Endert E., et al. Effects of acute and chronic interleukin-6 administration on thyroid hormone metabolism in humans. J. Clin. Endocrinol. Metab. 1994, 79: 1342–1346.
Corssmit E.P., Heyligenberg R., Endert E., Sauerwein H.P., Romijn J.A. Acute effects of interferon-alpha administration on thyroid hormone metabolism in healthy men. J. Clin. Endocrinol. Metab. 1995, 80: 3140–3144.
Sato K., Satoh T., Shizume K. Inhibition of 125I organification and thyroid hormone release by interleukin-1, tumor necrosis factor-alpha, and interferon-gamma in human thyrocytes in suspension culture. J. Clin. Endocrinol. Metab. 1990, 70: 1735–1743.
Nishikawa T., Yamashita S., Namba H. Interferon-gamma inhibition of human thyrotropin receptor gene expression. J. Clin. Endocrinol. Metab. 1993, 77: 1084–1089.
Boelen A., Platvoet-ter Schiphorst M.C., Bakker O., Wiersinga W.M. The role of cytokines in the lipopolysaccharide- induced sick euthyroid syndrome in mice: J. Endocrinol. 1995, 146: 475–483.
de Metz J., Romijn J.A., Endert E., Corssmit E.P.M., Sauerwein H.P. Administration of interferon-gamma in healthy subjects does not modulate thyroid hormone metabolism. Thyroid 2000, 10: 87–91.
Rasmussen A.K., Kayser L., Feldt-Rasmussen U., Bendtzen K. 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. J. Endocrinol. 1994, 143: 359–365.
Wiersinga W.M., Chopra I.J. Radioimmunoassay of thyroxine (T4), 3,5,3’-triiodothyronine (T3), 3,3’,5’-triiodothyronine (reverse T3, rT3), and 3,3’- diiodothyronine (T2): Methods Enzymol. 1982, 84: 272–303.
de Metz J., Sprangers F., Endert E., et al. Interferon-gamma has immunomodulatory effects with minor endocrine and metabolic effects in humans. J. Appl. Physiol. 1999, 86: 517–522.
Cherem H.J., Nellen H.H., Gordon B.F., Chong M., Lifshitz G.A. Thyroid function and abdominal surgery. A longitudinal study. Arch. Med. Res. 1992, 23: 143–147.
Calandra T., Baumgartner J.D., Grau G.E. Prognostic values of tumor necrosis factor/cachectin, interleukin-1, interferon- alpha, and interferon-gamma in the serum of patients with septic shock. Swiss-Dutch J5 Immunoglobulin Study Group. J. Infect. Dis. 1990, 161: 982–987.
Rossol S., Voth R., Laubenstein H.P. Interferon production in patients infected with HIV-1. J. Infect. Dis. 1989, 159: 815–821.
Wenisch C., Parschalk B., Narzt E., Looareesuwan S., Graninger W. Elevated serum levels of IL-10 and IFN-gamma in patients with acute Plasmodium falciparum malaria. Clin. Immunol. Immunopathol. 1995, 74: 115–117.
Kung A.W., Jones B.M., Lai C.L. Effects of interferon-gamma therapy on thyroid function, T-lymphocyte subpopulations and induction of autoantibodies. J. Clin. Endocrinol. Metab. 1990, 71: 1230–1234.
Boelen A., Schiphorst M.C., Wiersinga W.M. Relationship between serum 3,5,3’-triiodothyronine and serum interleukin- 8, interleukin-10 or interferon gamma in patients with nonthyroidal illness. J. Endocrinol. Invest. 1996, 19: 480–483.
Bellon J.M., Manzano L., Bernardos L. Cytokine levels after open and laparoscopic cholecystectomy. Eur. Surg. Res. 1997, 29: 27–34
Helmy S.A., Wahby M.A., El Nawaway M. The effect of anaesthesia and surgery on plasma cytokine production. Anaesthesia 1999, 54: 733–738.
Kato M., Suzuki H., Murakami M., Akama M., Matsukawa S., Hashimoto Y. Elevated plasma levels of interleukin-6, interleukin-8, and granulocyte colony-stimulating factor during and after major abdominal surgery. J. Clin. Anesth. 1997, 9: 293–298.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
de Metz, J., Romijn, J.A., Gouma, D.J. et al. Interferon-γ administration does not affect human thyroid hormone metabolism in the post-surgical euthyroid sick syndrome. J Endocrinol Invest 25, 315–320 (2002). https://doi.org/10.1007/BF03344011
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03344011