Interleukin-6 and its considerable role in the pathogenesis of thyrotoxicosis-related disturbances of bone turnover in postmenopausal women

Background: Thyrotoxicosis is more frequent in postmenopausal women than in the general population, effectively accelerating bone turnover. Interleukin-6 has been shown to be involved in the pathogenesis of bone disorders. Thus, the aim of the present study was to assess the role of IL-6 and its soluble receptor in the pathogenesis of thyrotoxicosis-related disturbances of bone turnover in oestrogen-deficient women. Material and methods: The study was carried out in 40 subjects with toxic nodular goitre in three groups: Group 1 &#8212; 13 premenopausal females, mean age 36 &#177; 15 years (PremTx&#8594;PremEu); Group 2 &#8212; 12 postmenopausal females, mean age 66 &#177; 14 years (PostTx&#8594;PostEu); and Group 3 &#8212; 15 males, mean age 45 &#177; 21 years (MTx&#8594;MEu). Overt thyrotoxicosis and euthyreosis after treatment with thyrostatics were confirmed by thyrotropin, free thyroxine and free triiodothyronin concentrations. Serum levels of bone turnover markers: TRACP5b and osteocalcin as well as serum IL-6 and IL-6sR were determined using ELISA kits. Results: TRACP5b/osteocalcin quotient was significantly elevated in the PostTx females compared to the PremTx women (p < 0.02). There was a positive correlation between serum TRACP5b and osteocalcin in the studied patients (R = 0.45, p < 0.001). Levels of serum IL-6 values were significantly elevated in PostTx: 3.0 (2.14&#8211;6.40) and MTx: 2.24 (1.60&#8211;5.10), compared to PremTx females: 1.39 (0.96&#8211;2.14) (p < 0.01 and p < 0.05 respectively). There were significant positive correlations between IL-6 and IL-6sR concentrations (R = 0.22, p < 0.05) and between IL-6sR and TRACP5b serum levels (R = 0.23, p < 0.05). Conclusions: The results of our study suggest that interleukin-6 plays a considerable role in the pathogenesis of thyrotoxicosis-related disturbances of bone turnover in oestrogen-deficient women. (Pol J Endocrinol 2011; 62 (4): 299&#8211;302)Wstęp: Nadczynność tarczycy występuje częściej u kobiet po menopauzie w porównaniu z populacją ogólną, skutecznie przyspieszając obrót kostny. Wykazano, że interleukina 6 (IL-6) odgrywa istotną rolę w regulacji obrotu kostnego. Uwzględniając ten fakt, celem obecnej pracy była próba oceny roli IL-6 i jej rozpuszczalnego receptora w patogenezie zaburzeń obrotu kostnego w przebiegu tyreotoksykozy u kobiet po menopauzie. Materiał i metody: Badanie przeprowadzono u 40 osób z nadczynnym wolem guzkowym w 3 grupach: 1 &#8212; 13 kobiet przed menopauzą w wieku 36 &#177; 15 lat (PremTx&#198;PremEu), 2 &#8212; 12 kobiet po menopauzie w wieku 66 &#177; 14 lat (PostTx&#198;PostEu) i 3 &#8212; 15 mężczyzn w wieku 45 &#177; 21 lat (MTx&#198;MEu). Stan czynnościowy tarczycy potwierdzono oznaczeniem TSH, fT3 i fT4 w surowicy. Markery obrotu kostnego: TRACP5b i osteokalcyna oraz IL-6 i IL-6sR w surowicy, oznaczono zestawami ELISA. Wyniki: Iloraz TRACP5b/osteokalcyna był istotnie zwiększony u kobiet PostTx w porównaniu z grupą PremTx (p < 0,02). Stwierdzono dodatnią korelację między TRACP5b i osteokalcyną (R = 0,45, p < 0,001). Stężenie IL-6 było istotnie zwiększone w grupie PostTx: 3,0 (2,14&#8211;6,40) i MTx: 2,24 (1,60&#8211;5,10) w porównaniu z odnotowanym u kobiet z grupy PremTx: 1,39 (0,96&#8211;2,14) (odpowiednio: p < 0,01 i p < 0,05). Wykazano istotną dodatnią korelację pomiędzy IL-6 i IL-6sR (R = 0,22, p < 0,05) oraz pomiędzy IL-6sR i TRACP5b (R = 0,23, p < 0,05). Wnioski: Podsumowując, wyniki obecnej pracy wskazują, że IL-6 odgrywa ważną rolę w patogenezie zaburzeń obrotu kostnego w przebiegu tyreotoksykozy u kobiet po menopauzie. (Endokrynol Pol 2011; 62 (4): 299&#8211;302

Serum interleukin-16 and RANTES during treatment of Graves&prime; orbitopathy with corticosteroids and teleradiotherapy

Introduction: To assess the usefulness of circulating IL-16 and RANTES measurements as markers of Graves&prime; orbitopathy (GO) activity and to estimate the role of these cytokines in GO pathogenesis. Material and methods: 42 individuals were divided into four groups: Group 1 comprised 15 euthyroid patients with clinical symptoms of GO who underwent corticosteroid therapy consisting of intravenous infusions of methylprednisolone (MP) and teleradiotherapy (TR); Group 2 comprised ten patients with hyperthyroid GD (Gtx); Group 3 comprised ten patients with GD in euthyreosis (Geu); and Group 4 comprised seven healthy volunteers age- and sex-matched to Groups 1&#8211;3. Serum samples were collected 24 hours before the first dose of MP, 24 hours after the first dose of MP, before TR, and at the end of therapy. Serum IL-16 and RANTES were determined by ELISA and TSH-Rab by RIA. Results: Serum IL-16 levels in patients with GO were significantly elevated at the end of therapy: 346 pg/mL (257&#8211;538) compared to IL-16 values before treatment: 250 ng/mL (211&#8211;337) and to the control group. RANTES serum concentrations did not significantly differ between studied groups, and immunosuppressive treatment did not influence its level. A negative correlation between TSH-Rab and RANTES was found in all studied groups (R = &#8211;0.32, p < 0.01). Conclusions: Our data suggests that IL-16 may exert an immunoregulatory effect in Graves&prime; orbitopathy. Serum measurements of both IL-16 and RANTES may be clinically useful; however, establishing their place in the diagnostics and treatment monitoring of GO needs further research. (Pol J Endocrinol 2012; 63 (2): 92&#8211;96)Wstęp: Ocena przydatności oznaczania krążącej IL-16 i RANTES jako wskaźników aktywności GO oraz określenie roli tych cytokin w patogenezie GO. Materiał i metody: 42 osoby w 4 grupach: 1 &#8212; 15 pacjentów z klinicznymi objawami orbitopatii w eutyreozie (GO), którzy poddali się leczeniu kortykosteroidami przy zastosowaniu podawanego dożylnie metylprednizolonu (MP) i teleradioterapii (TR); 2 &#8212; 10 pacjentów z chorobą Gravesa w nadczynności (Gtx); 3 &#8212; 10 pacjentów z chorobą Gravesa w eutyreozie (Geu); 4 &#8212; 7 zdrowych ochotników dobranych pod względem płci i wieku do grup 1.&#8211;3. Próbki krwi pobrano 24 h przed MP, 24 h po 1. dawce MP, przed TR i po zakończeniu leczenia. Stężenia IL-16 i RANTES w surowicy oznaczono metodą ELISA, a TSH-Rab &#8212; metodą RIA. Wyniki: Stężenie IL-16 w surowicy u pacjentów z GO było istotnie wyższe po zakończeniu terapii &#8212; 346 pg/ml (257&#8211;538) w porównaniu z wartością IL-16 przed leczeniem &#8212; 250 ng/ml (211&#8211;337) i w odniesieniu do grupy kontrolnej. Stężenie RANTES w surowicy nie różniło się istotnie między badanymi grupami i leczenie immunosupresyjne nie wpłynęło na jej wartość. Wykazano ujemną korelację między TSH-Rab i RANTES we wszystkich badanych grupach (R = &#8211;0,32; p < 0,01). Wnioski: Uzyskane dane wskazują, że IL-16 może wywierać immunomodulujący wpływ na przebieg orbitopatii. Zarówno oznaczenia IL-16, jak i RANTES w surowicy mogą być przydatne klinicznie, jednak ustalenie ich miejsca w diagnostyce i monitorowaniu leczenia GO wymaga dalszych badań. (Endokrynol Pol 2012; 63 (2): 92&#8211;96

Plasma levels of soluble tumor necrosis factor-α receptors are related to total and LDL-cholesterol in lean, but not in obese subjects

BACKGROUND: Tumor necrosis factor-α (TNFα) is a mediator of insulin resistance. Plasma levels of soluble TNFα receptors (sTNFR1 and sTNFR2) probably reflect paracrine action of the cytokine. TNFα is also a regulator of lipid metabolism, however, data about impact of obesity on the relationships between TNFα and plasma lipids remain controversial. AIM: The purpose of the present study was to examine the associations of TNFα system with plasma lipids in lean and obese subjects with normal glucose metabolism. METHODS: We examined 63 subjects, 33 lean (BMI<25 kg × m(-2)) and 30 with marked overweight or obesity (BMI>27.8 kg × m(-2)). Anthropometric and biochemical parameters were measured. Oral glucose tolerance test and euglycemic hyperinsulinemic clamp were also performed. RESULTS: Obese subjects were markedly more insulin resistant and had higher levels of both TNFα receptors. Total (TC) and LDL-cholesterol (LDL-C), triglycerides (TG) and non-esterified fatty acids (NEFA) were also higher in the obese group. In obese subjects, both receptors were significantly related to TG and HDL-cholesterol (HDL-C), while sTNFR2 was also associated with NEFA. All those correlations disappeared after controlling for insulin sensitivity. In lean subjects, both receptors were related to TC, HDL-C and LDL-C. In that group, sTNFR1 predicted values of all those parameters independently of BMI, plasma glucose and insulin, and insulin sensitivity. CONCLUSION: We conclude that TNFα receptors are associated with plasma lipids in different way in lean and in obese subjects. TNFα system is probably important in determining cholesterol levels in lean subjects, while in obese this effect might be masked by other metabolic abnormalities

The dust origin of the Broad Line Region and the model consequences for AGN unification scheme

We propose a very simple physical mechanism responsible for the formation of the Low Ionization Line part of the Broad Line Region in Active Galactic Nuclei. It explains the scaling of the Broad Line Region size with the monochromatic luminosity, including the exact slope and the proportionality constant, seen in the reverberation studies of nearby sources. The scaling is independent from the mass and accretion rate of an active nucleus. The mechanism predicts the formation of a dust-driven wind in the disk region where the local effective temperature of a non-illuminated accretion disk drops below 1000 K and allows for dust formation. We explore now the predictive power of the model with the aim to differentiate between this model and the previously proposed mechanisms of the formation of the Broad Line Region. We discuss the expected departures from the universal scaling at long wavelength, and the role of the inclination angle of the accretion disk in the source. We compare the expected line profiles with Mg II line profiles in the quasars observed by us with the SALT telescope. We also discuss the tests based on the presence or absence of the broad emission lines in low luminosity active galaxies. Finally, we discuss the future tests of the model to be done with expected ground-based observations and satellite missions.Comment: Based the talk presented during the COSPAR 2014 meeting, Advances in Space Research (in press

Circulating monocyte chemoattractant protein-1 in women with gestational diabetes.

Monocyte chemoattractant protein 1 (MCP-1) has been implicated as a key factor in the recruitment and activation of peripheral blood leukocytes in atherosclerotic lesions and adipose tissue. Elevated levels of circulating MCP-1 have been found in patients with type 1 and type 2 diabetes, as well as with coronary artery disease. In this study we compared serum MCP-1 concentrations between pregnant women with normal glucose tolerance (NGT), gestational diabetes mellitus (GDM) and non-pregnant healthy women. The group studied consisted of 62 patients with GDM (mean age 30.1 +/- 5.0 years) at 29.0 +/- 3.5 week of gestation, 64 pregnant women with NGT (mean age 30.0 +/- 4.7 years) at 29.2 +/- 2.9 week of gestation and 34 non-pregnant healthy women (mean age 29.8 +/- 4.7 years). Serum MCP-1 concentration was measured using an enzyme - linked immunosorbent assay. Median MCP-1 concentrations did not differ significantly between women with GDM (median 342.3 [interquartile range 267.9-424.4] pg/ml) and NGT (338.0 [274.7-408.2] pg/ml), but were markedly lower than those found in non-pregnant women (485.2 [409.6-642.4] pg/ml,

Role of interleukin-6 on RANKL-RANK/osteoprotegerin system in hypothyroid ovariectomized mice.

Postmenopausal women frequently develop hypothyroidism. Estrogen depletion is accompanied by an increase of IL-6, accelerating bone turnover. The influence of hypothyroidism on bone metabolism in postmenopausal women is poorly understood. The aim of the study was an attempt to clarify the role of interleukin-6 on RANKL-RANK/osteoprotegerin system in hypothyroid ovariectomized mice. The study was performed on 56, 12-13 weeks old, female mice: C57BL/6J (wild-type; WT) and C57BL/6JIL6-/-Kopf (IL-6 knock-out; IL6KO). The mice were randomly divided into 8 groups with 7 mice in each one: 1/ WT controls, 2/ IL6KO controls, 3/ WT hypothyroid mice, 4/ IL6KO hypothyroid mice, 5/ WT ovariectomized, 6/ IL6KO ovariectomized, 7/ WT ovariectomized hypothyroid mice and 8/ IL6KO ovariectomized hypothyroid mice. Experimental model of menopause was produced by bilateral ovariectomy carried out in 8-9 weeks old mice. Experimental model of hypothyroidism was induced by propylthiouracyl administration in driking water. The serum levels of TRACP 5b, osteocalcin, OPG and RANKL were determined by ELISA. Serum RANKL concentrations were elevated significantly in all groups of ovariectomized mice as compared to respective controls, but in a minor degree in IL6KO hypothyroid mice as compared to wild-type animals. Moreover sRANKL values were significantly lower in IL6KO as compared to WT controls and IL6KO PTU injected mice. Osteoprotegerin serum levels were decreased in all IL-6 deficient mice and in a highest degree in sham-operated hypothyroid mice. To sum up, the results of the present study suggest that estrogens deficit is a strong stimulus for RANKL-RANK/OPG pathway that breaks an inhibitory influence of hypothyroidism even in IL-6 deficient mice