Interleukin-1 receptor blockade does not affect endotoxin-induced changes in plasma thyroid hormone and thyrotropin concentrations in man.
Interleukin-1 (IL-1) has been implicated as a mediator of the euthyroid sick syndrome. The effects of IL-1 can be blocked by the naturally occurring IL-1 receptor antagonist (IL-1ra). In the present study, iv administration of endotoxin was used as a human model of the euthyroid sick syndrome. To assess the role of endogenous IL-1 in endotoxin-induced changes in plasma thyroid hormone and TSH concentrations, 18 healthy postabsorptive humans were studied on a control study day, followed 3 days later by a study day on which they were randomly assigned to one of three treatments: a 6-h infusion of recombinant human IL-1ra alone (133 mg/h), endotoxin alone (lot EC-5; 20 U/kg), or both endotoxin and IL-1ra. Administration of IL-1ra alone did not affect the plasma concentrations of thyroid hormones or TSH compared with those on the control day. Endotoxin injection was associated with decreases in T4 (P = 0.06 vs. the control day), free T4 (P = 0.02), T3 (P < 0.001), and TSH (P < 0.0001) and a rise in rT3 (P < 0.001), reproducing the major features of the euthyroid sick syndrome. Coinfusion of IL-1ra did not influence these endotoxin-induced changes. Our results suggest that endogenous IL-1 does not play an important role in the alterations in plasma thyroid hormone and TSH concentrations induced by mild endotoxemia in healthy humans.
van der Poll
T
T
Department of Surgery, Cornell University Medical College, New York, New York 10021, USA.
Van Zee
K J
KJ
Endert
E
E
Coyle
S M
SM
Stiles
D M
DM
Pribble
J P
JP
Catalano
M A
MA
Moldawer
L L
LL
Lowry
S F
SF
D000328:Adult; D004731:Endotoxins / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009994:Osmolar Concentration; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D013963:Thyroid Hormones / Q000097:blood*; D013972:Thyrotropin / Q000097:blood*; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood; D014285:Triiodothyronine, Reverse / Q000097:blood
D004731:Endotoxins; D017472:Receptors, Interleukin-1; D013963:Thyroid Hormones; D014284:Triiodothyronine; D014285:Triiodothyronine, Reverse; D013972:Thyrotropin; D013974:Thyroxine