Table 2.

Summary of the in vitro and in vivo effects of four main pro-inflammatory cytokines

	Evidence from in vitro data	Evidence from animal models	other interfering elements	Patients data
IL-1 beta	↓ iodide uptake in FRTL-5 and in porcine thyroid cells [57–59] ↓ T3 secretion in human thyrocytes [60], ↓ Tg mRNA expression in human thyrocytes [61, 97] ↓ TPO mRNA in Graves’ thyrocytes [63] ↓ induction of DIO1 mRNA [64] ↓ DIO1 activity in hepatocytes [65, 66] ↓TSH secretion in rat pituitary cells [69]	↓ TT4, TT3, TSH production in rats [67, 68]
TNF-α	↓ iodide uptake in FRTL-5 and Thyroid cancer cells [Spizweg et al. 1999, 77], ↓ Tg synthesis in human thyrocites [70] ↓ T3 secretion in human thyrocites [60], ↓ DIO1 activity [7, 71], ↓ basal and TSH-stimulated TPO and Tg gene expression in FRTL-5 cells and human normal thyroid cells [77] ↓ TSH synthesis in rat pituitary cells [74]	↓ TSH, TT3, TT4 ↓ hypothalamic TRH syntesis, ↓TSH glycosylation in mouse and rat models [57, 72]	↓ albumin production by rat hepatocytes(Perlmutter et al. 1986)	↓ serum T3 in cancer patients treated with recombinant human TNF-α (Feelders et al. 1999)
IL-6	↓ iodide uptake in FRTL-5 and thyroid cancer cells ↓ Tg synthesis in human thyrocites ↓ T3 secretion in human thyrocites [78, 79], ↑proliferation in human thyrocites, ↓ DIO1 mRNA [81] ↓ DIO1 and DIO2 activity [81] ↑ DIO3 activity [81] ↓ basal and TSH-stimulated TPO and Tg gene expression in FRTL-5 cells and human normal thyroid cells [80] ↑ expression of DIO2 in rat pituitary cells [74]		↓ hepatic synthesis of TBG, TTR, albumin [82, Ramadori et al. 1988)	Inverse correlation between IL-6 and FT3 levels [Bartalena et al. 1994] [Boelen et al. 1993,1995; Davies et al. 1996; Friberg et al. 2002) Intravenous injection of IL-6 given to healthy humans causes a transient decrease in serum T3 and an increase in rT3 [88]
IFN-γ	↑ iodide uptake, ↓thyroglobulin synthesis, ↓basal and TSH-stimulated TPO and Tg gene expression in FRTL-5 cells and human normal thyroid cells ↓proliferation of human thyroid cells ↑ iodide uptake [89], ↓ Tg synthesis [90] ↓ basal and TSH-stimulated TPO and Tg gene expression in FRTL-5 cells and human normal thyroid cells [90–94] ↓ proliferation of human thyroid cells [95] ↓DIO-1 activity in FRTL-5 [77]	Severe hypothyroidism in transgenic mice expressing IFN-γ in thyroid cells due to downregulation inhibition of the NIS gene [96]		No acute effect on circulating TSH, FT3, FT4 levels in critically ill patients after treatment with IFN-γ [98], higher risk of hypothyroidism in patients chronically treated [99]