A Study of the Serum Concentration of Tumor Necrosis Factor-α in Thyroidal and Nonthyroidal Illnesses*

Abstract

We have studied serum concentrations of immunoassayable tumor necrosis factor-alpha (TNF alpha) and iodothyronines (T4, T3, and rT3) in normal subjects (n = 16) and patients with nonthyroidal illnesses (NTI; n = 13), hyperthyroidism (n = 10), and hypothyroidism (n = 9). The mean (+/- SEM; femtomoles per mL) serum concentration of TNF alpha was 45 +/- 4.3 in normal subjects, 84 +/- 38 in NTI, 54 +/- 6.0 in hyperthyroidism, and 50 +/- 10 in hypothyroidism; the various values did not differ significantly from one another. Serum TNF alpha was well within the normal range in all NTI patients, except one patient with a brain glioma and infection in whom it was elevated (540 fmol/mL). There was no significant correlation between serum TNF alpha and serum T4, T3, or rT3 levels in NTI patients. Similarly, there was no correlation between serum TNF alpha and serum thyroid hormone (T3 or T4) levels when data in normal subjects were combined with those in NTI patients. The dialyzable fraction of T3 and the free T3 concentration did not correlate with serum TNF alpha levels. However, there was a tendency toward a positive correlation between dialyzable fraction of T4 and the serum concentration of TNF alpha in NTI (r = 0.54; n = 11; 0.05 greater than P less than 0.1). The relationship between these two parameters became more clear when data in normal subjects and NTI patients were combined for statistical analysis (r = 0.59; n = 22; P less than 0.005). The free T4 concentration correlated positively with serum TNF alpha levels whether the data in NTI patients were analyzed alone (r = 0.93; P less than 0.001) or in combination with data from normal subjects (r = 0.85; P less than 0.001). Our data suggest that circulating TNF alpha may contribute to elevated free T4 in NTI. However, it is not a universal or common factor in the pathogenesis of other alterations in serum thyroid hormone levels in NTI (euthyroid sickness syndrome).

A novel mechanism for the inhibition of type 2 iodothyronine deiodinase by tumor necrosis factor α: involvement of proteasomal degradation

“…IC50 of TNFα to inhibit (Bu) 2 cAMP-stimulated D2 activity in TCO-1 cells was approximately 1.0 ng/ mL. The effective dose of TNFα is comparable to that reported in the previous study [32] suggesting that the physiological concentration of TNFα is able to regulate T 3 production. Although (Bu) 2 cAMP stimulation of D2 activity sustained up to 24h, the prolonged treatment with TNFα suppressed (Bu) 2 cAMP-stimulated D2 activity to the basal level.…”

Proinflammatory cytokines inhibit the expression and function of human type I 5'-deiodinase in HepG2 hepatocarcinoma cells

“…Infusion of IL-1b produces a similar picture in experimental rats (32) and was shown to reduce hepatic 5 0 DI mRNA in mice (33). TNF-a levels have also been investigated in patients with SES, but were found to be within the normal range (34).…”

Role of cytokines in the pathogenesis of the euthyroid sick syndrome

“…Serum rT 3 concentration were normal in sleeping sickness (83). The relevance of TNF-a changes in NTI patients was questioned, based on the observation that serum concentration of the cytokine was elevated in only 1 of 13 NTI patients (84); no relationship was found between TNF-a and thyroid hormone concentrations, with the exception of a slight correlation with FT 4 values, possibly related to a TNF-a-induced increase in FFA levels (84) ( Table 3). An increase in serum IL-6 concentrations was reported in NTI patients, especially those with low T 3 concentration (83,(85)(86)(87) (Table 3).…”