PMID- 9781636
OWN - NLM
STAT- MEDLINE
DCOM- 19981029
LR  - 20190725
IS  - 0026-0495 (Print)
IS  - 0026-0495 (Linking)
VI  - 47
IP  - 10
DP  - 1998 Oct
TI  - Acute and delayed effects of a single-dose injection of interleukin-6 on thyroid 
      function in healthy humans.
PG  - 1289-93
AB  - 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.
FAU - Torpy, D J
AU  - Torpy DJ
AD  - 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.
FAU - Tsigos, C
AU  - Tsigos C
FAU - Lotsikas, A J
AU  - Lotsikas AJ
FAU - Defensor, R
AU  - Defensor R
FAU - Chrousos, G P
AU  - Chrousos GP
FAU - Papanicolaou, D A
AU  - Papanicolaou DA
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Metabolism
JT  - Metabolism: clinical and experimental
JID - 0375267
RN  - 0 (Interleukin-6)
RN  - 0 (Thyroxine-Binding Proteins)
RN  - 9002-71-5 (Thyrotropin)
RN  - WI4X0X7BPJ (Hydrocortisone)
SB  - IM
MH  - Adult
MH  - Body Temperature/drug effects
MH  - Female
MH  - Hemodynamics/drug effects
MH  - Humans
MH  - Hydrocortisone/blood
MH  - Interleukin-6/*pharmacology
MH  - Male
MH  - Thyroid Gland/*drug effects/physiology
MH  - Thyrotropin/blood
MH  - Thyroxine-Binding Proteins/analysis
EDAT- 1998/10/22 00:00
MHDA- 1998/10/22 00:01
CRDT- 1998/10/22 00:00
PHST- 1998/10/22 00:00 [pubmed]
PHST- 1998/10/22 00:01 [medline]
PHST- 1998/10/22 00:00 [entrez]
AID - S0026-0495(98)90338-9 [pii]
AID - 10.1016/s0026-0495(98)90338-9 [doi]
PST - ppublish
SO  - Metabolism. 1998 Oct;47(10):1289-93. doi: 10.1016/s0026-0495(98)90338-9.