Soluble cytokine receptors and the low 3,5,3'-triiodothyronine syndrome in patients with nonthyroidal disease.

Cytokines have been implicated in the pathogenesis of the low T3 syndrome during illness. This is supported by our recent observation of a strong negative relationship between serum T3 and serum interleukin-6 (IL-6) in nonthyroidal illness (NTI). In the last few years, soluble cytokine receptors and cytokine receptor antagonists have been discovered in human serum. These proteins have the potential to further regulate cytokine activity. Therefore, we now studied the association between serum T3 and serum levels of soluble tumor necrosis factor-alpha (sTNF alpha R p55 and sTNF alpha R p75), soluble interleukin-2 receptor (sIL-2R), and the interleukin-1 receptor antagonist (IL-1RA) in 100 consecutive hospital admissions with a wide variety of nonthyroidal diseases. Patients were divided into group A (T3, > or = 1.30 nmol/L; T4, > or = 75 nmol/L; n = 41), group B (T3, < 1.30 nmol/L; T4, > or = 75 nmol/L; n = 46), and group C (T3, < 1.30 nmol/L; T4, < 75 nmol/L; n = 13). Serum sTNF alpha R p55, sTNF alpha R p75, sIL-2R, and IL-1RA were lower in group A than in groups B and C [median values; sTNF alpha R p55, 1.25, 2.25, and 3.55 ng/mL (P < 0.001); sTNF alpha R p75, 2.02, 4.56, and 7.00 ng/mL (P < 0.001); sIL-2R, 184, 259, and 272 U/mL (P = 0.0004), respectively]. Serum IL-1RA levels were not different in the three groups (median values, 122, 193, and 258 pg/mL, respectively). Taking all patients together, a significant negative relation was found among serum T3 and sTNF alpha p55 (r = -0.59; P < 0.0001), sTNF alpha R p75 (r = -0.55; P < 0.0001), sIL-2R (r = -0.54; P < 0.0001), IL-1RA (r = -0.38; P = 0.001), and IL-6 (r = -0.56; P < 0.0001). A remarkable high correlation (r = -0.70; P < 0.0001) was found between serum T3 and a newly designed total score based on the summation of serum levels of IL-6 and the four soluble cytokine receptor proteins. IL-6 and the four cytokine receptor proteins were all significantly related to each other. Stepwise multiple regression indicated IL-6 and sTNF alpha R p75 as independent determinants of T3 [serum T3 = 2.09-0.32ln (sTNF alpha R p75) -0.15ln (IL-6); r = 0.70]. The variability in serum T3 was accounted for 35% by changes in ln (sTNF alpha R p75) and 14% by changes in ln (IL-6).(ABSTRACT TRUNCATED AT 400 WORDS)