Dataset Information

Circulating TNF-Alpha and IL-6 Concentrations and TNF-Alpha -308 G?>?A Polymorphism in Children with Premature Adrenarche.

ABSTRACT: Premature adrenarche (PA), the early rise in adrenal androgen production leading to prepubertal signs of androgen action, has been connected with adverse metabolic features. The metabolic syndrome is characterized by low-grade inflammation which in turn is associated with increases in circulating proinflammatory cytokines, like tumor necrosis factor-alpha (TNF-?) and interleukin-6 (IL-6). We tested the hypothesis that serum concentrations of TNF-? and IL-6 are increased in PA by studying 73 children with PA and 98 age- and gender-matched controls. Serum TNF-? and IL-6 concentrations were measured using a multiplex bead array. The subjects were genotyped for the TNF-? gene -308 G?>?A polymorphism (known to affect TNF-? gene transcription), and genotype-phenotype associations were studied. The mean serum TNF-? concentration was higher in the PA than control children (20.4 vs. 18.4?pg/ml, P?=?0.048), whereas there was no significant difference in the mean serum IL-6 concentrations between the study groups. The difference in TNF-? was not explained by excess body weight in the PA subjects as the difference remained significant after BMI-adjustment (P?=?0.038). In the PA group, TNF-? concentration was not associated with metabolic-endocrine features, but high IL-6 was associated with lower birth weight. There was no difference in the genotype distribution of the TNF-? gene -308 G?>?A polymorphism between the PA and control groups. In conclusion, PA was associated with increased serum TNF-? concentrations which, unexpectedly, were not connected with BMI or insulin resistance. The TNF-? gene -308 G?>?A polymorphism does not seem to be associated with the development of PA.

SUBMITTER: Utriainen P

PROVIDER: S-EPMC3356042 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Circulating TNF-Alpha and IL-6 Concentrations and TNF-Alpha -308 G > A Polymorphism in Children with Premature Adrenarche.

Utriainen Pauliina P Jääskeläinen Jarmo J Gröhn Oskari O Kuusisto Johanna J Pulkki Kari K Voutilainen Raimo R

Frontiers in endocrinology 20101124

Premature adrenarche (PA), the early rise in adrenal androgen production leading to prepubertal signs of androgen action, has been connected with adverse metabolic features. The metabolic syndrome is characterized by low-grade inflammation which in turn is associated with increases in circulating proinflammatory cytokines, like tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). We tested the hypothesis that serum concentrations of TNF-α and IL-6 are increased in PA by studying 73 chil ...[more]

PMID: 22654787

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Project description:Background and objectiveThe association between TNF-α -308 G/A polymorphism and COPD remains controversial due to insufficiently strict study designs and small group sizes among different studies. In the present study, a meta-analysis update which followed a stricter procedure was performed to obtain a clearer understanding of this association.MethodsA comprehensive database search was conducted to identify the case-control studies published up to July 2015 which reported an association between the TNF-α -308 G/A polymorphism and COPD risk. Data were extracted to calculate pooled odds ratios with 95% confidence intervals under the most appropriate genetic and allelic models. Sensitivity was analyzed, and heterogeneity as well as publication bias was assessed.ResultsThirty-eight eligible studies, comprising 3,951 COPD cases and 5,110 controls, were included in this study, among which 22 studies comprising 2,067 COPD cases and 2,167 controls were performed in Asians, and 16 studies comprising 1,884 COPD cases and 2,943 controls were in non-Asians. The overall result showed that TNF-α -308 G/A polymorphisms were significantly associated with increased COPD risk in both the codominant genetic and allelic models. Individuals with the GA or AA genotype were more susceptible to COPD development than those with the GG genotype. In addition, individuals with the AA genotype were more susceptible to developing COPD than those with the GA genotype. The subgroup analysis stratified by ethnicity supported the results in Asians but not in non-Asians. However, no association was found between TNF-α -308 G/A polymorphisms and COPD susceptibility either in Asians or in non-Asians in the meta-analysis conducted with restriction to former/current smokers.ConclusionThe present meta-analysis suggested that the TNF-α -308 G/A polymorphism was associated with an increased risk of COPD among Asians but not in non-Asians. Furthermore, individuals with the AA genotype of TNF-α -308 were more susceptible to developing COPD.

Project description:Malaria, blood-borne filarial worms and intestinal parasites are all endemic in Gabon. This geographical co-distribution leads to polyparasitism and, consequently, the possibility of immune-mediated interactions among different parasite species. Intestinal protozoa and helminths could modulate antimalarial immunity, for example, thereby potentially increasing or reducing susceptibility to malaria. The aim of the study was to compare the cytokine levels and cytokine ratios according to parasitic profiles of the population to determine the potential role of co-endemic parasites in the malaria susceptibility of populations. Blood and stool samples were collected during cross-sectional surveys in five provinces of Gabon. Parasitological diagnosis was performed to detect plasmodial parasites, Loa loa, Mansonella perstans, intestinal helminths (STHs) and protozoan parasites. Nested PCR was used to detect submicroscopic plasmodial infection in individuals with negative blood smears. A cytometric bead array was used to quantify interleukin (IL)-6, IL-10 and tumour necrosis factor (TNF)-α in the plasma of subjects with different parasitological profiles. Median IL-6 and IL-10 levels and the median IL-10/TNF-α ratio were all significantly higher among individuals with Plasmodium (P.) falciparum infection than among other participants (p<0.0001). The median TNF-α level and IL-10/IL-6 ratio were higher in subjects with STHs (p = 0.09) and P. falciparum-intestinal protozoa co-infection (p = 0.04), respectively. IL-6 (r = -0.37; P<0.01) and IL-10 (r = -0.37; P<0.01) levels and the IL-10/TNF-α ratio (r = -0.36; P<0.01) correlated negatively with age. Among children under five years old, the IL-10/TNF-α and IL-10/IL-6 ratios were higher in those with intestinal protozoan infections than in uninfected children. The IL-10/TNF-α ratio was also higher in children aged 5-15 years and in adults harbouring blood-borne filariae than in their control counterparts, whereas the IL-10/IL-6 ratio was lower in those aged 5-15 years with filariae and intestinal parasites but higher in adults with intestinal parasitic infections. Asymptomatic malaria is associated with a strong polarization towards a regulatory immune response, presenting high circulating levels of IL-10. P. falciparum/intestinal protozoa co-infections were associated with an enhanced IL-10 response. Immunity against malaria could differ according to age and carriage of other parasites. Helminths and intestinal protozoa can play a role in the high susceptibility to malaria currently observed in some areas of Gabon, but further investigations are necessary.

Dataset Information

Circulating TNF-Alpha and IL-6 Concentrations and TNF-Alpha -308 G?>?A Polymorphism in Children with Premature Adrenarche.

Publications

Circulating TNF-Alpha and IL-6 Concentrations and TNF-Alpha -308 G > A Polymorphism in Children with Premature Adrenarche.

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