Hellenic National Diabetes Center Athens, Greece
George P. Chrousos and Dimitris A. Papanicolaou
Developmental Endocrinology Branch National Institute of Child Health and Human Development, NIH Bethesda, Maryland
Corticosteroid-binding globulin (CBG), a glucoprotein of hepatic origin, binds cortisol and modifies its bioavailability (1). Interleukin-6 (IL-6) dose-dependently inhibits CBG messenger RNA expression and protein secretion by hepatoblastoma-derived (HepG2) cells (2). This is consistent with the presence of a nuclear factor-IL-6-binding site in the rat CBG gene promoter, also conserved in the promoter of the human CBG gene (3). These findings suggest that CBG is a negative acute phase reactant protein.
We recently reported the results of a dose-response study of single subcutaneous injections of recombinant human IL-6 on pituitary hormone production and glucose metabolism in healthy male volunteers (4, 5). We hereby provide evidence from these volunteers that supports the inhibitory effect of IL-6 on CBG production. We measured CBG (6), cortisol, and the positive acute phase reactant C-reactive protein (CRP) at baseline, then at 24 h, 48 h, and 7 days after the IL-6 injection in three volunteers who received 0.3 µg/kg of IL-6, a dose that did not activate the hypothalamic-pituitary-adrenal (HPA) axis and in three volunteers who received 3.0 µg/kg of IL-6, a dose that strongly stimulated the HPA axis (4).
Plasma IL-6 levels reached a peak of 22 ± 5 pg/mL and
290 ± 38 pg/mL for the two doses respectively, between 2 and
4 h after the injection, and returned to baseline by 24 h in
both groups. While the 0.3 µg/kg dose did not appreciably influence
plasma CBC levels, the 3.0 µg/kg dose caused a significant and
persistent decrease in CBC levels that lasted at least 48 h, but
returned to baseline by 7 days (Fig. 1).The corresponding CRP levels showed a mirror image response, increasing
significantly by 24 h (from 0.77 ± 0.06 mg/dL to 9.8 ±
1.01 mg/dL, P < 0.01), remaining elevated at 48 h
(6.0 ± 1.24, P < 0.05 vs. baseline)
and returning to normal by 7 days (0.75 ± 0.05 mg/dL). Cortisol
levels, despite the dramatic response observed during the first 4
h after the IL-6 injection (4), were at baseline by 24 h and
remained so thereafter.
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Footnotes
Address correspondence to: Constantine Tsigos, M.D., Hellenic National Diabetes Center, 3 Ploutarchou Street, 106 75 Athens, Greece.
Received April 23, 1998.
References