Increased interleukin-12 plasma concentrations in both, insulin-dependent and non-insulin-dependent diabetes mellitus

Winkler, Gábor; Dworák, O.; Salamon, Ferenc; Salamon, Dániel; Speer, G; Cseh, Károly

doi:10.1007/s001250050935

Cited by 43 publications

(28 citation statements)

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“…Th2 associated mediators were not affected by autoantibody status (IL-13), tended to be increased (IL-5, IL-10), or were decreased in serum levels (MCP-1). These findings do not bear on the bias toward Th1-type cytokines in type 1 diabetes as reported by many groups (33)(34)(35)(36)(37)(38)(39)(40)(41)(42). However, among patients with type 1 diabetes, a multiple islet autoantibody positivity does not associate with a further enhanced systemic Th1 bias.…”

Section: Discussioncontrasting

confidence: 53%

An Association of Autoantibody Status and Serum Cytokine Levels in Type 1 Diabetes

Hanifi-Moghaddam¹,

Schloot²,

Kappler³

et al. 2003

Diabetes

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At onset of type 1 diabetes, the islet autoantibody status of patients has been reported to predict progression of the disease. We therefore tested the hypothesis that the systemic immunoregulatory balance, as defined by levels of circulating cytokines and chemokines, is associated with islet autoantibody status. In 50 patients with recent-onset type 1 diabetes, antibodies to GAD and insulinoma-associated antigen 2 (IA-2) were analyzed by radioimmunoassay; cytoplasmic islet cell antibodies were determined by indirect immunofluorescence.

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Section: Discussioncontrasting

confidence: 53%

An Association of Autoantibody Status and Serum Cytokine Levels in Type 1 Diabetes

Hanifi-Moghaddam¹,

Schloot²,

Kappler³

et al. 2003

Diabetes

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“…Rothe et al have emphasized the pathogeneic role of the IL-12 in insulin-dependent diabetes mellitus of the non-obese diabetic mice. Moreover, IL-12 proved to be a potent inhibitor of angiogenesis and may also contribute to the pathogenesis of diabetic retinopathy more likely as a part of the consecutive immunological response mechanisms rather than a predisposing factor [40]. Moreover, the IL-12 that was implicated in the pathogenesis of DR in type 1 diabetes [12] was not associated with PDR in Caucasians with type 2 diabetes in our study.…”

Section: Discussionmentioning

confidence: 43%

Polymorphisms of interleukin-4, -10 and 12B genes and diabetic retinopathy

et al. 2011

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In diabetic retinopathy (DR) and other angiogenesis-associated diseases, increased levels of cytokines, inflammatory cells, and angiogenic factors are present. We investigated the hypothesis that rs2243250 polymorphism of the interleukin 4 (IL-4) gene or rs1800896 polymorphism of the interleukin 10 (IL-10) gene, and rs3212227 polymorphism of the 3’ untranslated region (3’ UTR) of the interleukin-12 p40 gene (IL12B) may be associated with the development of proliferative diabetic retinopathy (PDR) in Caucasians with type 2 diabetes (DM2). This cross sectional case — control study included 189 patients with PDR and 187 patients with type 2 diabetes without PDR. Polymorphisms rs1800896 of the IL-10 gene, rs2243250 of the IL-4 gene, and rs3212227 of IL12B gene were analyzed by ARMS -PCR and RFLP -PCR methods. Multivariate analysis demonstrated the GG genotype of the rs1800896 polymorphism of the IL-10 gene to be associated with increased risk for PDR (OR=1.99; 95% CI=1.11–3.57; P=0.02), whereas the TT genotype of the rs2243250 polymorphism of the IL-4 gene and the AA genotype of the rs3212227 polymorphism of the IL-12 gene were not independent risk factors for PDR. Our findings suggest that the genetic variations at the IL-10 promoter gene might be a genetic risk factor for PDR in Caucasians with type 2 diabetes.

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“…However, the IL-12p40 homodimer has also been shown to antagonize IL-12p70 activity in murine (49) cells and human cell lines (50), which would argue for a rather antiinflammatory function for this subunit. Because associations have been described between increased serum levels of IL-12p70 and insulin resistance in humans (51,52), a reduction of IL-12p40 in serum could result in increased action of IL-12p70 and subsequent insulin resistance. In an attempt to translate our findings to systemic IL-12p40 levels, we measured serum IL-12p40 levels in 12 lean and 12 obese individuals.…”

Section: Discussionmentioning

confidence: 99%

Adipocytes Modulate the Phenotype of Human Macrophages through Secreted Lipids

Klein-Wieringa

Andersen

Kwekkeboom

et al. 2013

The Journal of Immunology

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Previous studies have shown accumulation and an enhanced proinflammatory profile of macrophages in adipose tissue of obese mice, indicating the presence of an interaction between adipocytes and macrophages in this tissue. However, the consequences of this interaction in humans are yet incompletely understood. In this study, we explored the modulating effects of adipocytes on the phenotype of macrophages in humans and studied the possible molecular pathways involved. Adipocyte-conditioned media (ACM) treatment of macrophages for 48 h strongly reduced the LPS-induced IL-12p40 secretion by macrophages, whereas the production of TNF-α and other cytokines remained largely unaffected. This effect was independent of the source of adipocytes. Interestingly, the level of inhibition correlated directly with body mass index (BMI) of the adipocyte donor. Because adipocytes release many different cytokines, adipokines, and lipids, we have separated the protein and lipid fractions of ACM, to obtain insight into the molecular nature of the soluble mediators underlying the observed effect. These experiments revealed that the inhibitory effect resided predominantly in the lipid fraction. Further studies revealed that PGE2 and linoleic and oleic acid were potent inhibitors of IL-12p40 secretion. Interestingly, concentrations of these ACM-derived lipids increased with increase in BMI of the adipocyte donor, suggesting that they could mediate the BMI-dependent effects of ACM. To our knowledge, these results provide first evidence that obesity-related changes in adipose tissue macrophage phenotype could be mediated by adipocyte-derived lipids in humans. Intriguingly, these changes appear to be different from those in murine obesity.

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Increased interleukin-12 plasma concentrations in both, insulin-dependent and non-insulin-dependent diabetes mellitus

Cited by 43 publications

References 0 publications

An Association of Autoantibody Status and Serum Cytokine Levels in Type 1 Diabetes

An Association of Autoantibody Status and Serum Cytokine Levels in Type 1 Diabetes

Polymorphisms of interleukin-4, -10 and 12B genes and diabetic retinopathy

Adipocytes Modulate the Phenotype of Human Macrophages through Secreted Lipids

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