Modulation of Macrophage Function by Thyroxine, Triiodothyronin, and Thyroid-Stimulating Hormone (TSH) in Euthyroid Sick Syndrome (I)

  • Chao, Tzu-Chieh (PI)
  • Lin, Jen-Der (CoPI)

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details


Evidence has been accumulated that there is an interaction between the thyroid hormones and the immune system. In addition to the role in hormonal homeostasis, TSH and thyroid hormones are known to be important for normal development of the thymus, for thymus-mediated immune responses, and antibody responses. Thyroidectomy or thiouracil-induced hypothyroidism decreases lymphoid organ weight, numbers of circulating lymphocytes, antibody responses, and mitogen-induced proliferative responses in animals. T3 or T4 administration enhanced antibody and mitogen responses. Hyperthyroidism is also found to enhance phagocytosis and nitric oxide synthase activity in Kupffer cells. Macrophages in the hypothyroid rats with streptococcal cell wall-induced arthritis produce more macrophage inflammatory protein-1α (MIP-1α) and IL-1β, but T4-treated rats show significant inhibition of MIP-1α and IL-1β. The effects of thyroid hormones on respiratory burst of macrophages are controversial. In addition to the generation of respiratory burst, thyroid hormones inhibit or enhance phagocytic activity or respiratory buerst of macrophages. Euthyroid sick syndrome, with low serum levels of T3 and/or T4, is commonly seen in sepsis and other non-thyroid critical illness. Absence of thyroid hormones significantly increases mortality in the rats with sepsis and thyroxine replacement prevents the increased mortality from sepsis. Macrophages are important immune cells not only interacting with lymphocytes but also having anti-microbial and tumoricidal activities. Current studies of the effects of thyroid hormones on macrophage function are limited and the results are somewhat controversial. Therefore, continued exploration of the regulatory effects of thyroid hormones on macrophage function is necessary. Our general hypothesis is that T3, T4, and TSH modulate the function of macrophages. The specific aims of this study are: 1. To characterize the function of macrophages in euthyroid sick syndrome, hyperthyroidism or hypothyroidism. 2. To explore the mechanisms of modulatory effects of thyroid hormones on macrophages. In this study, we will examine generation of hydrogen peroxide and nitric oxide, inducible nitric oxide synthase (iNOS) activity, phagocytosis, macrophage-mediated cytotoxicity, as well as release of tumor necrosis factor-α, interleukin-1β, interleukin-6, and transforming growth factor-β1. Expression of TNF-α mRNA, IL-1β mRNA, IL-6 mRNA, TGF-β1 mRNA, and iNOS mRNA will be examined using semi-quantitative RT-PCR. Transcription factor NFκB and its inhibitory protein IκB, prostagaldin E2, leukotriene B4, intracellular cAMP, expression of cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) will be studied to disclose the regulatory mechanisms. The first year project of this proposal has been approved(NSC 92-2314-B-182-071: 92/08/01 – 93/07/31)and our preliminary results showed that high concentrations of T3 and T4 inhibited nitric oxide production by rat peritoneal macrophages in the absence or presence of LPS. On the other hand, T4 either inhibited or enhanced H2O2 generation depending on the concentrations used. We believe that our study will not only provide better understanding of the relationship between thyroid hormones and immunity, but also help develop appropriate prophylactic methods in preventing high morbidity and mortality rates in euthyroid sick syndrome.

Project IDs

Project ID:PC9308-0990
External Project ID:NSC93-2314-B182-060
Effective start/end date01/08/0431/07/05


  • euthyroid sick syndrome
  • hydrogen peroxide
  • hyperthyroidism
  • hypothyroidism
  • nitric oxide
  • phagocytosis
  • thyroxine
  • triiodothyronine
  • thyroid stimulating hormone
  • tumor necrosis factor-α
  • interleukin-1β
  • interleukin-6
  • transforming growth factor-β1


Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.