Torpy D J, Tsigos C, Lotsikas A J, Defensor R, Chrousos G P, Papanicolaou D A
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, and the Nursing Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892-1862, USA.
Metabolism. 1998 Oct;47(10):1289-93. doi: 10.1016/s0026-0495(98)90338-9.
Interleukin-6 (IL-6) is produced in response to inflammatory and noninflammatory stress and acts as the principal regulator of the acute-phase protein response. IL-6 stimulates the hypothalamic-pituitary-adrenal axis and may be involved in the thyroid function abnormalities observed in nonthyroidal illness (NTI). This study examined the effects of single-dose IL-6 (3 microg/kg subcutaneously [s.c.]) in healthy human subjects: 19 received IL-6 and 13 received control saline injection. The dose of IL-6 was chosen on the basis of previous studies indicating that the peak IL-6 level after injection reaches concentrations observed with major stress such as abdominal surgery. Plasma levels of thyrotropin (TSH), free thyroxine (FT4), total T4, 3,5-3'-L-triiodothyronine (T3), 3,3'-5'-L-triiodothyronine or reverse T3 (rT3), and thyroxine-binding globulin (TBG) were measured over a 4-hour period and 24 hours after IL-6 injection. Plasma TSH levels were 27% lower 240 minutes after IL-6 relative to control levels (0.93 +/- 0.10 v 1.28 +/- 0.18 mIU/mL, P = .001), but recovered by 24 hours. Plasma FT4 was elevated at 240 minutes compared with the controls (1.16 +/- 0.04 v 1.03 +/- 0.03 ng/dL, P = .0002). T4 levels were also elevated at 240 minutes (7.8 +/- 0.36 v 7.05 +/- 0.37 microg/dL, P = .0003). TBG levels were not significantly changed at this time point. At 24 hours, T3 levels were 19% lower than the control values (87.6 +/- 5.1 v 108.5 +/- 5.4 ng/dL, P = .0002); plasma rT3 levels were elevated by 21% compared with control levels (30.6 +/- 1.7 v 24.3 +/- 1.3 ng/dL, P = .002), while FT4 levels returned to normal. The changes in T3/rT3 levels were reminiscent of the pattern observed in NTI that may be due to inhibition of type-1 5'-deiodinase. Cortisol levels were greatly elevated after IL-6 compared with control values; peak levels were observed 120 minutes after IL-6 injection (28.7 +/- 1.6 v 9.5 +/- 1.0 ng/dL, P < .0001). This elevation in cortisol may have contributed to the suppression of TSH levels and inhibition of type-1 5'-deiodinase activity. Alternatively, IL-6 may have suppressed TSH secretion via a direct suprapituitary action. The elevation of T4 and FT4 levels may have been due to inhibition of T4 degradation at the liver and/or by direct action of IL-6 on the thyroid gland. These findings demonstrate the potent effects of IL-6 on thyroid hormone metabolism in healthy individuals, and suggest that IL-6 may act directly or indirectly at two or more sites on thyroid hormone secretion and metabolism.
白细胞介素-6（IL-6）是机体对炎症和非炎症应激作出反应时产生的，它是急性期蛋白反应的主要调节因子。IL-6刺激下丘脑-垂体-肾上腺轴，可能参与非甲状腺疾病（NTI）中观察到的甲状腺功能异常。本研究检测了单剂量IL-6（3微克/千克皮下注射）对健康人体受试者的影响：19人接受IL-6注射，13人接受对照生理盐水注射。IL-6的剂量是根据先前的研究选定的，先前研究表明注射后IL-6的峰值水平达到腹部手术等重大应激时观察到的浓度。在注射IL-6后的4小时和24小时内，检测血浆促甲状腺激素（TSH）、游离甲状腺素（FT4）、总T4、3,5,3'-L-三碘甲状腺原氨酸（T3）、3,3',5'-L-三碘甲状腺原氨酸或反式T3（rT3）以及甲状腺素结合球蛋白（TBG）的水平。与对照水平相比，IL-6注射后240分钟时血浆TSH水平降低了27%（0.93±0.10对1.28±0.18毫国际单位/毫升，P = 0.001），但在24小时时恢复正常。与对照组相比，240分钟时血浆FT4升高（1.16±0.04对1.03±0.03纳克/分升，P = 0.0002）。T4水平在240分钟时也升高（7.8±0.36对7.05±0.37微克/分升，P = 0.0003）。此时TBG水平无显著变化。在24小时时，T3水平比对照值低19%（87.6±5.1对108.5±5.4纳克/分升，P = 0.0002）；血浆rT3水平比对照水平升高了21%（30.6±1.7对24.3±1.3纳克/分升，P = 0.002），而FT4水平恢复正常。T3/rT3水平的变化让人联想到NTI中观察到的模式，这可能是由于1型5'-脱碘酶受到抑制。与对照值相比，IL-6注射后皮质醇水平大幅升高；在IL-6注射后120分钟观察到峰值水平（28.7±1.6对9.5±1.0纳克/分升，P < 0.0001）。皮质醇的这种升高可能导致了TSH水平的抑制和1型5'-脱碘酶活性的抑制。或者，IL-6可能通过直接的垂体上作用抑制TSH分泌。T4和FT4水平的升高可能是由于肝脏中T4降解的抑制和/或IL-6对甲状腺的直接作用。这些发现证明了IL-6对健康个体甲状腺激素代谢有显著影响，并表明IL-6可能在甲状腺激素分泌和代谢的两个或更多位点直接或间接发挥作用。
