Increased serum concentrations of FFA,
bilirubin, and carboxyl-methyl-propyl-furanpropionic
acid, accumulating in
chronic renal failure in direct relationship with serum
creatinine, have all been implicated in the pathogenesis of the
low T3 syndrome during illness.
Cytokines may also be involved in the
sick euthyroid syndrome. In contrast to
interleukin-1 (IL-1) and
tumor necrosis factor-alpha,
IL-6 is usually detectable in serum during illness and acts as a systemic
hormone. We studied the association between serum T3 and
IL-6 in consecutive hospital admissions with a wide variety of medical conditions. 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
IL-6 levels in groups C and B were higher than those in group A (median values 59, 39, and 9 U/mL, respectively; P < 0.01). Serum
creatinine and
bilirubin/
albumin ratios were similar in the three groups, but the FFA/
albumin ratio in group C was higher than in group A (P < 0.05). When all patients were analyzed together, serum T3 was negatively correlated to serum
IL-6 (r = -0.56; P < 0.001),
bilirubin/
albumin ratio (r = -0.29; P = 0.004), and FFA/
albumin ratio (r = -0.21; P = 0.03), but not with
creatinine (r = -0.16; P = 0.11). Stepwise multiple regression resulted in the following equation: serum T3 = 2.13-0.18ln(IL-6)-0.15ln(
creatinine)-0.094ln(
bilirubin /
albumin) (r = 0.61). The variability in serum T3 was accounted for 28% by ln(IL-6), 5% by ln(
creatinine), and 4% by ln(
bilirubin/
albumin). FFA/
albumin did not contribute in this respect. We conclude that the
low T3 syndrome in nonthyroidial illness is associated with high serum
IL-6 levels. However, even when
IL-6 is assumed to play a causative role, the variation of serum T3 in NTI-patients remains largely unexplained.