The Role of Thyroid Hormone in the Innate and Adaptive Immune Response during Infection

In the past decades, there has been growing evidence for a functional interaction between the thyroid hormone and the immune system. This article provides an overview of the mechanisms by which thyroid hormones affect the innate and adaptive immune response during infection. The influence of thyroid hormone on the most important players of the innate [neutrophils, macrophages, natural killer (NK) cells, and dendritic cells (DCs)] and adaptive immune system (B-and T-lymphocytes) is reviewed here based on both clinical and preclinical studies. The effects of modulation of the immune system by drugs, such as monoclonal antibodies, tyrosine kinase inhibitors, and interferons on thyroid function, are beyond the scope of this article. Thyroid hormones regulate the activity of neutrophils which is reflected by higher numbers of neutrophils outside the bloodstream and enhanced activity of the respiratory burst following stimulation with thyroid hormone. Hyperthyroidism affects neutrophil function to a larger extent than hypothyroidism. In addition to neutrophil function, macrophage function is strongly affected by thyroid hormones, with triiodothyronine having a pro-inflammatory effect in these cells. NK cell proliferation and cytotoxic activity are also dependent on thyroid hormone levels. Finally, thyroid hormones enhance DC proliferation and maturation. In the adaptive immune system, a hyperthyroid state leads to increased activation of lympho-cytes. This effect of thyroid hormone is mediated by various factors including NF-κB and protein kinase C signaling pathways and the β-adrenergic receptor. In general, a hyperthyroid state leads to a more activated immune system whereas hypothy-roidism leads to a less activated immune system.