Relation between serum interleukin‐6 and thyroid hormone concentrations in 270 hospital in‐patients with non‐thyroidal illness

Davies, P.H. O'Connor; Black, E. G.; Sheppard, M. C.; Franklyn, Jayne A.

doi:10.1046/j.1365-2265.1996.668489.x

Cited by 96 publications

(65 citation statements)

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“…IL-6 levels were elevated in serum of all NTI patients and correlated strongly with serum T 3 , which is in agreement with previous reports (Boelen et al 1993, Davies et al 1996. IL-6 has been shown to contribute to the pathogenesis of NTI but the mechanisms have not yet been elucidated (Boelen et al 1996).…”

Section: Rαsupporting

confidence: 81%

Triiodothyronine affects the alternative splicing of thyroid hormone receptor alpha mRNA

Timmer

Bakker²,

Wiersinga

2003

Journal of Endocrinology

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The c-erbA gene encodes two thyroid hormone receptors, TR 1 and TR 2, that arise from alternative splicing of the TR pre-mRNA. TR 2 is not able to bind triiodothyronine (T 3 ) and acts as a weak antagonist of TRs. It has been suggested that the balance of TR 1 to TR 2 is important in maintaining homeostasis. Here, we study the effect of thyroid hormone on the splicing of TR under various conditions in HepG2 cells. First, T 3 was added to HepG2 cells that endogenously express TR . This resulted in a decrease in the TR 1:TR 2 mRNA ratio after the addition of 10 8 M or 10 7 M T 3 . Then, HepG2 cells were incubated with sera from hypothyroid or hyperthyroid patients. Sera from hyperthyroid patients (n=6) decreased the TR 1:TR 2 ratio compared with HepG2 cells incubated with sera from euthyroid patients (n=8). Sera from hypothyroid patients (n=6) had no effect on the TR 1:TR 2 ratio but supplementation with T 3 caused a decrease in the ratio. Finally, we tested sera from patients with nonthyroidal illness (NTI; n=17) which showed no effect on TR splicing when compared with controls. Free thyroxine levels in sera from hypo-, eu-, and hyperthyroid patients, but not that of NTI patients, were negatively correlated (P,0·01) to the TR 1:TR 2 ratio. We next studied the expression of the splicing factors hnRNP A1 and ASF/SF2 (SF2) in relation to the splicing of the TR gene. In HepG2 cells incubated with NTI sera a negative relationship was found between the ratio of hnRNP A1:SF2 and the TR 1:TR 2 ratio. A high hnRNP A1:SF2 ratio is associated with the use of the distal 5 -splice site. The splicing direction should then change towards TR 2, which is indeed the case. Rev-ErbA, which is partly complementary to TR 2 and could therefore interfere in the splicing process, did not relate to the TR 1:TR 2 ratio.In conclusion, high T 3 levels induce a low TR 1:TR 2 ratio which could protect the cell from excessive T 3 -induced gene expression. In vivo, this might be a mechanism to keep tissues relatively euthyroid during high serum T 3 levels.

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Section: Rαsupporting

confidence: 81%

Triiodothyronine affects the alternative splicing of thyroid hormone receptor alpha mRNA

Timmer

Bakker²,

Wiersinga

2003

Journal of Endocrinology

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“…Pro-inflammatory cytokines such as tumour necrosis factor-α [24], interleukin-1 [25] and 6 (IL-6) [26] have a major role in thyroid hormone imbalances. Serum IL-6 levels are often increased in NTIS and have been inversely correlated with T3 levels and TSH suppression [27]. The C-reactive protein is an inflammatory protein used in clinical decision-making produced by the liver in response to IL-6 [20].…”

Section: Discussionmentioning

confidence: 99%

The influence of body mass index and low-grade systemic inflammation on thyroid hormone abnormalities in patients with type 2 diabetes

et al. 2013

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The relaTionship between diabetes mellitus (DM) and thyroid hormones (TH) is a complex one. It is known that TH levels affect not only glycaemic control but also hepatic and muscular insulin resistance and play a major role in energy homeostasis [1]. Both hypothyroidism and thyrotoxicosis have been shown to increase insulin resistance [2]. Decompensated hyperthyroidism can worsen glycaemic control and predispose patients to diabetic ketoacidosis [3].On the other hand, patients with DM may show abstract. Previous reports highlight the role of systemic inflammation in the genesis of non-thyroidal illness syndrome and type 2 diabetes mellitus (T2DM). Our objective was to assess whether body mass index and the low-grade systemic inflammation would be associated with changes in thyroid hormone metabolism in patients with type 2 diabetes. This was a cross-sectional study of 104 subjects; 52 patients with type 2 diabetes and 52 in a control group, paired by age, gender and body mass index. We measured total (T) and free (F) thyroxine (T4) and triiodothyronine (T3), reverse T3 (rT3), the ratios FT3/rT3, FT3/FT4 and FT4/rT3, clinical parameters (age, gender, diabetes duration and complications, body mass index, waist circumference, hypertension, HbA1c), and high sensitivity C-reactive protein. Patients with DM presented lower levels of TT4 (p=0.006), TT3 (p<0.001) and FT3 (p<0.001) and higher of FT4 (p<0.001), waist circumference (p=0.047) and C-reactive protein (p<0.001). Body mass index was inversely correlated with FT4 (p=0.036) and TT3 (p=0.008). C-reactive protein was positively correlated with rT3 (p=0.001) and inversely with FT4/rT3 (p<0.001) and FT3/rT3 (p=0.014). Body mass index was an independent predictor for FT4 (B=-0.011, p=0.029) and TT3 levels (B=-1.118, p=0.003). Inflammation predicted the FT4/rT3 ratio (B=-0.190, p<0.001). C-reactive protein (B=0.235, p<0.001) and body mass index (B=-0.008, p=0.047) were independent predictors for rT3. In conclusion, type 2 diabetes was associated with a low T3 state. Body mass index and the low-grade systemic inflammation are related to the non-thyroidal illness syndrome in these patients, possibly by altering the activity of peripheral deiodinases.Key words: Diabetes mellitus, Low T3, Inflammation, Non-thyroidal illness syndrome abnormalities in serum TH levels in the absence of intrinsic disease of the thyroid axis. These are similar to those present in critically ill patients with the non-thyroidal illness syndrome (NTIS), such as low serum triiodothyronine (T3) and thyroxine (T4) levels and elevated reverse T3 (rT3), with concurrent normal serum TSH levels [4,5]. This finding is more frequent in those with poor glycaemic control, especially when HbA1c levels are above 10.5-11% [6] and are reversible upon restoration of adequate metabolic control [7]. Although classically related to glycaemic control, the pathophysiology of TH abnormalities in patients with DM has never been fully investigated. Previous reports highlight the role of systemic inflammation in the genes...

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“…A temporal relationship between IL-6 and thyroid hormone variations was observed in the post-surgery period, since the increase in serum IL-6 concentration occurred early and preceded the decrease in serum T 3 concentration both in adults (91) and in children undergoing cardiopulmonary bypass (92). A recent evaluation of 270 inpatients with NTI, while confirming changes in IL-6 levels and their relationship with variations in serum thyroid hormone concentrations, showed that the IL-6 increase was modest in patients with acute or chronic renal disorders, in spite of the concomitant decrease in serum thyroid hormone concentrations, suggesting that, at least in this form of NTI, IL-6 is not the only or most important causative factor responsible for alterations in thyroid hormone metabolism (93).…”

Section: European Journal Of Endocrinology (1998) 138mentioning

confidence: 99%

Role of cytokines in the pathogenesis of the euthyroid sick syndrome

Bartalena

Bogazzi

Brogioni

et al. 1998

European Journal of Endocrinology

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Relation between serum interleukin‐6 and thyroid hormone concentrations in 270 hospital in‐patients with non‐thyroidal illness

Cited by 96 publications

References 0 publications

Triiodothyronine affects the alternative splicing of thyroid hormone receptor alpha mRNA

Triiodothyronine affects the alternative splicing of thyroid hormone receptor alpha mRNA

The influence of body mass index and low-grade systemic inflammation on thyroid hormone abnormalities in patients with type 2 diabetes

Role of cytokines in the pathogenesis of the euthyroid sick syndrome

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