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Christian Herder

Publications and source records attributed to Christian Herder.

At least 19 recordsLinked to original sources
PubMed2026

Large-scale multi-omics enhance risk prediction for type 2 diabetes.

BACKGROUND: Polygenic risk scores (PRS), metabolomics, and proteomics have each shown promise in improving type 2 diabetes risk prediction, but their combined utility beyond established clinical models remains unclear. We aimed to evaluate whether integrating multi-omics biomarkers enhances 10-year type 2 diabetes risk prediction beyond single-omics extensions and the clinical Cambridge Diabetes Risk Score (CDRS), which includes HbA1c measurements. METHODS: We analysed data from 42,840 UK Biobank participants without diagnosed diabetes at baseline. The study population was split into a derivation set (Phase 1 metabolomics release, N&#x2009;=&#x2009;23,108) to fit models and an independent validation set (Phase 2 release, N&#x2009;=&#x2009;19,732) to evaluate performance. Data for a PRS for type 2 diabetes, 11 metabolites, and 15 proteins were added to the CDRS to develop multi-omics prediction models. Model performance was evaluated using Harrell's C-index and the net reclassification index (NRI). RESULTS: During 10 years of follow-up, 1090 participants developed incident type 2 diabetes. Among individual omics layers, proteomics contributed the greatest improvement in predictive performance, increasing the C-index from 0.862 (clinical CDRS) to 0.884 (&#x394;C-index; + 0.022; P&#x2009;<&#x2009;0.001), with a continuous NRI of 42.0%. The full multi-omics model further significantly increased the C-index compared to a model combining the clinical CDRS with proteomics data (C-index, 0.891; &#x394;C-index; + 0.007; P&#x2009;<&#x2009;0.001). CONCLUSION: Integrating proteomics, metabolomics, and a diabetes-PRS into a clinical model substantially improves type 2 diabetes risk prediction beyond single-omics extensions. Several of the selected proteins and metabolites are on cardiovascular disease pathways, highlighting the link between diabetes and cardiovascular risk. However, the C-index difference between the proteomics extended and full multi-omics extended models is small, and the clinical models extended with proteomics data would be easier to translate into routine care because it needs only the measurement of 15 proteins. External validation and cost-effectiveness analyses are needed to support clinical adoption.

Humans↗
PubMed2006

Relationship between adipocyte size and adipokine expression and secretion.

CONTEXT: Adipocytes are known to release a variety of factors that may contribute to the proinflammatory state characteristic for obesity. This secretory function is considered to provide the basis for obesity-related complications such as type 2 diabetes and atherosclerosis. OBJECTIVE: To get a better insight into possible underlying mechanisms, we investigated the effect of adipocyte size on adipokine production and secretion. DESIGN, PATIENTS, AND MAIN OUTCOME MEASURES: Protein secretion and mRNA expression in cultured adipocytes separated according to cell size from 30 individuals undergoing elective plastic surgery were investigated. RESULTS: The mean adipocyte volume of the four fractions ranged from 205 +/- 146 to 1.077 +/- 471 pl. There were strong linear correlations for the secretion of adipokines over time. Secretion of leptin, IL-6, IL-8, TNF-alpha, monocyte chemoattractant protein-1, interferon-gamma-inducible protein 10, macrophage inflammatory protein-1beta, granulocyte colony stimulating factor, IL-1ra, and adiponectin was positively correlated with cell size. After correction for cell surface, there was still a significant difference between fraction IV (very large) and fraction I (small cells), for leptin, IL-6, IL-8, monocyte chemoattractant protein-1, and granulocyte colony-stimulating factor. In contrast, antiinflammatory factors such as IL-1ra and adiponectin lost their association after correction for cell surface area comparing fraction I and IV. In addition, there was a decrease of IL-10 secretion with increasing cell size. CONCLUSIONS: The results clearly suggest that adipocyte size is an important determinant of adipokine secretion. There seems to be a differential expression of pro- and antiinflammatory factors with increasing adipocyte size resulting in a shift toward dominance of proinflammatory adipokines largely as a result of a dysregulation of hypertrophic, very large cells.

Adipocytes↗
PubMed2006

The DREAM trial.

Explore the source record for details and available documents.

Clinical Trials as Topic↗
PubMed2006

Calpain-10 variants and haplotypes are associated with polycystic ovary syndrome in Caucasians.

PCOS is known to be associated with an increased risk of T2DM and has been proposed to share a common genetic background with T2DM. Recent studies suggest that the Calpain-10 gene (CAPN10) is an interesting candidate gene for PCOS susceptibility. However, contradictory results were reported concerning the contribution of certain CAPN10 variants, especially of UCSNP-44, to genetic predisposition to T2DM, hirsutism, and PCOS. By means of MALDI-TOF MS technique, we genotyped an expanded single nucleotide polymorphism panel, including the CAPN10 UCSNP-44, -43, -56, ins/del-19, -110, -58, -63, and -22 in a sample of 146 German PCOS women and 606 population-based controls. Statistical analysis revealed an association between UCSNP-56 and susceptibility to PCOS with an odds ratio (OR) of 2.91 (95% CI=1.51-5.61) for women carrying an AA genotype compared with GG. As expected, the 22-genotype of the ins/del-19 variant, which is in high linkage disequilibrium (r2=0.98) with UCSNP-56, was also significantly associated (OR=2.98, 95% CI=1.55-5.73). None of the additionally tested variants alone showed any significant association with PCOS. A meta-analysis including our study (altogether 623 PCOS cases and 1,224 controls) also showed significant association only with ins/del-19. The most common haplotype TGG3AGCA was significantly associated with a lower risk for PCOS (OR=0.487, P=0.0057). In contrast, the TGA2AGCA haplotype was associated with an increased risk for PCOS (OR=3.557, P=0.0011). By investigating a broad panel of CAPN10 variants, our results pointed to an allele dose-dependent association of UCSNP-56 and ins/del-19 with PCOS.

Adult↗
PubMed2006

Increased concentrations of C-reactive protein and IL-6 but not IL-18 are independently associated with incident coronary events in middle-aged men and women: results from the MONICA/KORA Augsburg case-cohort study, 1984-2002.

OBJECTIVE: We performed a prospective case-cohort study in initially healthy, middle-aged men and women from the MONICA/KORA Augsburg studies conducted between 1984 and 2002 to assess the role of IL-18 in comparison with IL-6 and CRP in the prediction of incident coronary heart disease (CHD). METHODS AND RESULTS: Concentrations of IL-18 were measured in 382 case subjects with incident CHD and 1980 noncases. Mean follow-up was 11 years. Baseline concentrations of IL-18 were slightly higher in cases than in noncases (172.4 [1.0] versus 161.3 [1.0] pg/mL, respectively; P=0.114), but were clearly elevated for C-reactive protein (CRP) and IL-6 in cases compared with noncases. In multivariable analyses, accounting for classical cardiovascular risk factors and inflammatory markers, no statistically significant association was seen between increased concentrations of IL-18 and incident CHD both in men (hazard ratio [HR] and 95% confidence intervals [CIs] comparing extreme tertiles, 1.20; 95% CI, 0.85 to 1.69), and in women (HR, 1.25; 95% CI, 0.67 to 2.34). However, in this population increased concentrations of CRP and IL-6 were found to be independent predictors of future CHD events, even after multivariable adjustment. CONCLUSIONS: Elevated concentrations of CRP and IL-6, but not IL-18, were independently associated with risk of CHD in subjects from an area with moderate absolute risk.

Adult↗
PubMed2006

Chemokines and incident coronary heart disease: results from the MONICA/KORA Augsburg case-cohort study, 1984-2002.

OBJECTIVE: The chemokines monocyte chemoattractant protein-1 (MCP-1/CCL2), interleukin-8 (IL-8/CXCL8), and interferon-gamma-inducible protein-10 (IP-10/CXCL10) have been reported to be involved in the development of atherosclerosis and type 2 diabetes. The aim of this study was to assess whether elevated systemic levels of these chemokines precede coronary events. METHODS AND RESULTS: We investigated MCP-1, IL-8, and IP-10 serum levels in a case-cohort design based on data from 381 individuals (294 men, 87 women) with and 1977 individuals (1006 men, 971 women) without incident coronary heart disease (CHD) from the prospective, population-based MONICA/KORA Augsburg study (1984 to 2002). The mean follow-up time was 11.0 years. Baseline concentrations were significantly higher in cases compared with noncases (P < or = 0.001 for all chemokines). MCP-1 and IL-8 remained associated with CHD risk after adjustment for age, sex, and survey with hazard ratios (95% confidence intervals) comparing extreme tertiles of 1.39 (1.05 to 1.84) for MCP-1 and 1.48 (1.10 to 1.99) for IL-8. However, adjustment for further cardiovascular and immunologic risk factors attenuated the observed associations, and they became nonsignificant. CONCLUSIONS: Elevated systemic levels of the chemokines MCP-1, IL-8, and IP-10 precede CHD but do not represent independent risk factors. Thus, the associations are less pronounced than previously shown for type 2 diabetes.

Case-Control Studies↗
PubMed2006

IL-6 promoter polymorphisms and quantitative traits related to the metabolic syndrome in KORA S4.

Interleukin-6 (IL-6) is a pleiotropic cytokine which has been proposed as "cytokine for gerontologists" and linked to age-related metabolic disturbances such as the metabolic syndrome or type 2 diabetes. Polymorphisms located in the promoter region of IL-6 have been reported to be involved in the regulation of IL-6 transcription. This study investigates whether IL-6 promoter variants -174 G/C and -573 G/C are associated with quantitative traits related to the metabolic syndrome (International Diabetes Federation criteria) in a population of normoglycemic subjects (n=878) from the latest KORA survey (KORA S4). Genotyping was performed using MALDI-TOF MS. Besides lower height (p=0.01) the -174 CC genotype was independently associated with lower waist (p=0.002) and hip (p=0.01) circumferences in men. Furthermore, the -174 CC genotype was associated with BMI (p=0.004) when adjusted for waist and hip circumference. The present study does not suggest associations with further components of the metabolic syndrome. The association with height seems to be the central factor indicating an influence of IL-6 on growth through impaired bone metabolism. However, the complex relationships need further investigation.

Aged↗
PubMed2006

Is inflammation a causal chain between low socioeconomic status and type 2 diabetes? Results from the KORA Survey 2000.

Low socioeconomic status (SES) is associated with type 2 diabetes. Inflammatory markers like C-reactive protein (CRP) are predictive of diabetes. It is unclear, whether inflammation may be a mechanism linking low SES to type 2 diabetes. In the population-based KORA Survey 2000, 766 men and 710 women aged 55 to 74 years were randomly selected in the Augsburg region (Southern Germany). An index for SES was defined using education, occupation, and income. In women but not in men, increased CRP concentrations were found with lower SES (p<0.01). This significant trend was no longer observed after adjusting for BMI and waist circumference (p=0.23). Low SES was significantly associated with the age-adjusted odds of having type 2 diabetes both in men (OR; 95%CI: 1.35; 1.14-1.60) and in women (2.01; 1.37-2.96). The risk of having diabetes associated with low SES was only slightly changed after adjusting for CRP, which was itself significantly related to diabetes. In multivariate analyses, adjusting for age, obesity, physical activity, smoking, alcohol intake, and CRP, low SES yielded only a borderline statistical significance in women (p=0.07), whereas no significant association with diabetes remained in men (p=0.14). After CRP was dropped from the full model, there was no change in the OR obtained for low SES (men: 1.30; 0.92-1.83; women: 1.54; 0.97-2.45). Low SES was not related to prediabetes (IFG, IGT), whereas CRP was significantly associated with diabetes precursors. In conclusion, inflammation appears not to play a major role linking low SES and type 2 diabetes in the elderly population.

Aged↗
PubMed2006

Inflammation in metabolic syndrome and type 2 diabetes: Impact of dietary glucose.

Chronic overnutrition combined with a lack of exercise is the main cause for the rapidly increasing prevalence of overweight and obesity. It seems accepted that adipositis (macrophage infiltration and inflammation of adipose tissue in obesity) and systemic low grade inflammation affect the pathogenesis of the metabolic syndrome or type 2 diabetes mellitus (T2DM). Therefore, modern weight reduction programs additionally focus on strategies to attenuate the inflammation state. Exercise is one major factor, which contributes to the reduction of both the incidence of T2DM and inflammation, and the immunomodulatory effects of exercise are supported by similarly beneficial effects of dietary changes. In this context, glucose is the most extensively studied nutrient and current investigations focus on postprandial glucose-induced inflammation, one possible reason why hyperglycemia is detrimental. Indeed, glucose may modulate the mRNA expression and serum concentrations of immune parameters but these alterations rapidly normalize in normoglycemic subjects. In case of an impaired metabolic state, however, postprandial hyperglycemia increases magnitude and duration of systemic inflammatory responses, which probably promotes the development of T2DM and of cardiovascular disease.

Cytokines↗
PubMed2006

Systemic monocyte chemoattractant protein-1 concentrations are independent of type 2 diabetes or parameters of obesity: results from the Cooperative Health Research in the Region of Augsburg Survey S4 (KORA S4).

OBJECTIVE: Data on the relevance of monocyte chemoattractant protein (MCP)-1 in the pathophysiology of type 2 diabetes (T2D) and obesity are inconsistent. Since MCP-1 is produced by adipocytes and has been postulated to be involved in macrophage infiltration into adipose tissue, we wanted to test whether serum MCP-1 levels were correlated with T2D or obesity. DESIGN AND METHODS: Out of 1653 individuals aged 55 to 74 years participating in the population-based KORA Survey S4 (KORA/Cooperative Health Research in the Region of Augsburg) in Southern Germany, 236 patients with T2D, 242 subjects with impaired glucose tolerance and 244 normoglycaemic controls matched for age and sex were analysed for circulating MCP-1 concentrations. RESULTS: MCP-1 serum concentrations were not associated with impaired glucose tolerance, type 2 diabetes or several parameters of obesity. Moreover, systemic MCP-1 levels were not significantly correlated with all but one (fasting triglycerides) of the biochemical markers tested. CONCLUSIONS: Our data indicate that MCP-1 levels are not associated with T2D and that the contribution of fat mass to systemic MCP-1 protein might be low, suggesting that the possible local pathogenic role of MCP-1 may not be reflected by increased systemic levels of MCP-1.

Aged↗
PubMed2006

Systemic immune mediators and lifestyle changes in the prevention of type 2 diabetes: results from the Finnish Diabetes Prevention Study.

The Finnish DPS (Diabetes Prevention Study) demonstrated that lifestyle intervention, aimed at increasing physical activity, improving diet, and decreasing body weight, reduced the incidence of type 2 diabetes in individuals with overweight and impaired glucose tolerance by 58%. Here, we studied which immunological markers at baseline predicted subsequent type 2 diabetes and whether there are immunologically defined subsets of subjects who are more or less responsive to the protective effects of lifestyle intervention. We randomly assigned 522 participants to a control group (n = 257) or a lifestyle intervention group (n = 265). Immunological parameters at baseline included high-sensitivity C-reactive protein (CRP), serum amyloid A, interleukin-6, regulated on activation normal T-cell expressed and secreted (RANTES), macrophage migration inhibitory factor (MIF), and soluble intercellular adhesion molecule. In the control group, CRP was the best immunological predictor for progression to overt type 2 diabetes. In the intervention group, progression to type 2 diabetes was significantly higher in subjects with the highest RANTES concentrations and was lower in subjects with the highest MIF levels. Ratios of RANTES to MIF in the upper tertile were highly predictive of incident type 2 diabetes in the intervention group (P = 0.006), whereas the association was less pronounced in the control group (P = 0.088). Thus, systemic concentrations of immune mediators appear to be associated with the progression to type 2 diabetes and the prevention of type 2 diabetes by lifestyle changes.

Anthropometry↗
PubMed2006

IL6 gene promoter polymorphisms and type 2 diabetes: joint analysis of individual participants' data from 21 studies.

Several lines of evidence indicate a causal role of the cytokine interleukin (IL)-6 in the development of type 2 diabetes in humans. Two common polymorphisms in the promoter of the IL-6 encoding gene IL6, -174G>C (rs1800795) and -573G>C (rs1800796), have been investigated for association with type 2 diabetes in numerous studies but with results that have been largely equivocal. To clarify the relationship between the two IL6 variants and type 2 diabetes, we analyzed individual data on >20,000 participants from 21 published and unpublished studies. Collected data represent eight different countries, making this the largest association analysis for type 2 diabetes reported to date. The GC and CC genotypes of IL6 -174G>C were associated with a decreased risk of type 2 diabetes (odds ratio 0.91, P = 0.037), corresponding to a risk modification of nearly 9%. No evidence for association was found between IL6 -573G>C and type 2 diabetes. The observed association of the IL6 -174 C-allele with a reduced risk of type 2 diabetes provides further evidence for the hypothesis that immune mediators are causally related to type 2 diabetes; however, because the association is borderline significant, additional data are still needed to confirm this finding.

Case-Control Studies↗
PubMed2006

Hypoadiponectinemia and proinflammatory state: two sides of the same coin?: results from the Cooperative Health Research in the Region of Augsburg Survey 4 (KORA S4).

OBJECTIVE: Previous studies have yielded conflicting results on the association of adiponectin levels and inflammation. Low systemic concentrations of adiponectin, as well as elevated levels of immune mediators, represent risk factors for the development of type 2 diabetes and coronary artery disease. The major aim of this cross-sectional study was to investigate the interdependence of hypoadiponectinemia and low-grade systemic inflammation. RESEARCH DESIGN AND METHODS: The study sample consisted of 606 participants aged 55-74 years (244 with normal glucose tolerance, 242 with impaired glucose tolerance, and 120 with newly diagnosed type 2 diabetes) of the population-based KORA S4 (Cooperative Health Research in the Region of Augsburg Survey 4; 1999-2001). Systemic concentrations of adiponectin and a wide range of anthropometric, metabolic, and inflammatory variables were available for analyses. The association of adiponectin with 15 immunological markers, including leukocyte count, acute-phase proteins, cytokines, cytokine receptors, and chemokines, was assessed using univariable and multivariable models. RESULTS: No evidence for a significant correlation between adiponectin and all immunological parameters except eotaxin could be found after multivariable adjustments, whereas multiple strong correlations with obesity and metabolic factors were present. CONCLUSIONS: From these data, we conclude that hypoadiponectinemia and a proinflammatory state are largely independent from each other.

Adiponectin↗
PubMed2006

Association of systemic concentrations of macrophage migration inhibitory factor with impaired glucose tolerance and type 2 diabetes: results from the Cooperative Health Research in the Region of Augsburg, Survey 4 (KORA S4).

OBJECTIVE: Macrophage migration inhibitory factor (MIF) is a central cytokine in innate immunity. MIF expression can be regulated by glucose and insulin, but data on the association with type 2 diabetes are sparse. The aim of this study was to test whether MIF is associated with impaired glucose tolerance (IGT) and type 2 diabetes and whether these associations are independent of metabolic and immunological risk factors and to compare the associations of MIF and IGT/type 2 diabetes with those of C-reactive protein (CRP) and interleukin-6 (IL-6) with IGT/type 2 diabetes. RESEARCH DESIGN AND METHODS: The Cooperative Health Research in the Region of Augsburg/Kooperative Gesundheitsforschung im Raum Augsburg, Survey 4 (KORA S4) is a population-based survey performed in Southern Germany (1999-2001). Of 1,653 participants aged 55-74 years, 236 patients with type 2 diabetes, 242 subjects with IGT, and 244 normoglycemic control subjects matched for age and sex were included in this cross-sectional study. Serum concentrations of MIF were measured by enzyme-linked immunosorbent assay. RESULTS: Serum MIF concentrations are highly increased in individuals with IGT and type 2 diabetes. The associations of MIF with IGT and type 2 diabetes were independent of classical risk factors and of CRP and IL-6 and were much stronger before and after multivariate adjustment than the associations of CRP and IL-6 with IGT and type 2 diabetes. CONCLUSIONS: Our data suggest that elevations of systemic MIF concentrations precede the onset of type 2 diabetes. This finding may be relevant because MIF has been reported to contribute to the development of type 2 diabetes-related diseases such as atherosclerosis and cancer.

Aged↗
PubMed2005

Differential expression of chemokines, risk of stable coronary heart disease, and correlation with established cardiovascular risk markers.

OBJECTIVE: We investigated the association of several chemokines with the risk of stable coronary heart disease (CHD) in a large case-control study after adjustment for other established risk factors. Furthermore, we analyzed their correlation with various acute-phase proteins, inflammation-associated cytokines, and an adhesion molecule. METHODS AND RESULTS: We included 312 patients aged 40 to 68 years with angiographically confirmed and stable CHD and 472 age- and gender-matched controls in this study. The main outcome measure was the odds ratio (OR) for CHD associated with increased levels of interferon (INF)-inducible protein of 10 kd (IP-10), interleukin (IL)-8, regulated on activation normal T-cell expressed and secreted (RANTES), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammation protein 1alpha (MIP-1alpha), or eotaxin determined by rigidly evaluated sandwich ELISAs. Serum levels of IP-10 and IL-8 were higher, and serum levels of RANTES were lower in CHD patients when compared with age- and gender-matched controls. In addition, values in the second and top tertile of IP-10 and IL-8 were associated with an increased OR for CHD when compared with values in the bottom tertile [OR for IP-10 (top tertile) was 2.62 (95% CI, 1.79 to 3.85) in the age- and gender-adjusted model and 1.93 (95% CI, 1.23 to 3.04) in the fully adjusted model, and for IL-8, the OR was 1.77 (95% CI, 1.20 to 2.59) and 1.53 (95% CI, 0.98 to 2.39), respectively]; increased RANTES values were associated with a lower OR for CHD [OR, 0.67 (95% CI, 0.47 to 0.96) and 0.61 (95% CI, 0.40 to 0.94)]. Furthermore, positive correlations of IP-10 and IL-8 with several acute-phase proteins or inflammation-associated cytokines were evident, and positive correlations for IP-10 plasma viscosity and intercellular adhesion molecule 1 were also present. CONCLUSIONS: The current study suggests that there may be no universal upregulation of chemokines in CHD-associated inflammation but different upregulation of IP-10 and IL-8 versus downregulation of RANTES; there was no clear disease association for MCP-1, MIP-1alpha, or eotaxin.

Acute-Phase Proteins↗
PubMed2005

Sex differences in the relation of body composition to markers of inflammation.

OBJECTIVE: It has been suggested that low-grade systemic inflammation is associated with obesity and that this association might be modified by sex. METHODS AND RESULTS: We performed a cross-sectional analysis among 641 men and 597 women aged 55-74 years who participated in the population-based KORA Survey 2000, conducted in the area of Augsburg, Germany. Measures of both total (fat mass, body mass index) and abdominal adiposity (waist circumference (WC), waist to hip ratio (WHR)) were highly correlated with markers of systemic inflammation (C-reactive protein (CRP), serum amyloid A (SAA), fibrinogen (FIB), interleukin-6 (IL-6)) in men and in women. Significant associations persisted when the effect of lifestyle factors was taken into account. In multivariable linear regression analysis, a considerably higher percentage of variability in inflammatory markers was explained by body composition in women compared to men. Furthermore, the relevance of single body composition variables varied by sex. In women, fat mass in % explained the highest percentage of the variability of circulating acute-phase proteins (18.2% for CRP, 7.2% for SAA, 6.1% for FIB, all p-values < 0.001), whereas in men, WHR explained the highest percentage of the variability (6.2% for CRP, 2.3% for SAA, 1.8% for FIB, all p-values < 0.001). For IL-6, WC explained the highest percentage of the variability in women (3.7%, p < 0.001) and in men (1.8%, p < 0.001). CONCLUSION: Adiposity is strongly associated with low-grade systemic inflammation in men and in women but the association is considerably stronger in women, especially for CRP. Thus, weight reduction as a means to prevent a state of subclinical inflammation might be particularly effective in women.

Adiposity↗
PubMed2005

Effects of a single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin, given at post-puberty, in senescent mice.

2,3,7,8-Tetrachlorodibenzo-p-dioxin is a well-known immunosuppressive environmental pollutant. TCDD interferes with physiological signaling of the arylhydrocarbon receptor, leading to cell-specific changes in gene transcription and cell differentiation. With respect to the immune system, the T-cell lineage and B-cell lineages are particularly affected. Although a single dose given to mice is excreted within weeks, these changes in differentiation may have long-term consequences for immune competence. We studied the effects of a single dose of TCDD given to young mice on some parameters of their immune system after they had aged almost to the end of their lifespan. Groups of 15 mice were given either 2.5 microg TCDD/kg b.w. or 25 microg TCDD/kg b.w. at the age of 8-12 weeks, and were analyzed between 16 and 21 months of age. Survival was equal in all groups. Blood glucose levels did not differ, and glucose tolerance after oral challenge was normal in old control mice and TCDD-exposed mice. No differences in the frequencies of B-cells, T-cells, or NK-cells were detectable. TCDD-exposed mice at both doses had a significantly higher titer of IgM compared to controls. Histological examination of pancreas, liver, kidney, spleen, and lungs yielded no differences, except for the lungs, where a significantly higher number of animals displayed activated BALT. In conclusion, our data suggest that a single dose of TCDD in young mice is correlated to activated secondary lymphoid tissues and high IgM titers. Both findings are congruent with a weakened immune system.

Aging↗