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Inflamm-aging indicates the chronic inflammatory state resulting from increased secretion of proinflammatory cytokines and mediators such as IL-6 in the elderly. Our principle objective was to identify cell types that were affected with aging concerning IL-6 secretion in the murine model. We compared IL-6 production in spleen cells from both young and aged mice and isolated several types of cells from spleen and investigated IL-6 mRNA expression and protein production. IL-6 protein productions in cultured stromal cells from aged mice spleen were significantly high compared to young mice upon LPS stimulation. IL-6 mRNA expression level of freshly isolated stromal cells from aged mice was high compared to young mice. Furthermore, stromal cells of aged mice highly expressed IL-6 mRNA after LPS injection in vivo. These results suggest that stromal cells play a role in producing IL-6 in aged mice and imply that they contribute to the chronic inflammatory condition in the elderly.

Peyer's patches (PPs) are potential sites where specific mucosal immune responses and oral tolerance are induced. The unique features of these immune responses are thought to occur in micromilieu and are largely affected by antigen-presenting cells (APCs) such as dendritic cells. In this study, we investigated the cytokine profiles induced by the activation of CD4(+) T cells of PPs. PP cells from TCR transgenic mice secreted greater amounts of IL-5 and IL-6 than spleen cells after antigenic stimulation. IL-5 was mainly produced by PP non-T cells, whereas IL-6 was secreted by PP CD4(+) cells. PPs contained two major populations including naïve and memory/activated CD4(+) cells; both populations secreted IL-6 upon activation. We also found that CD4(+)/CD62L(hi) naïve cells from PPs secreted a greater amount of IL-6 after stimulation than those from the spleen. Furthermore, subtraction and qPCR analyses revealed that PP CD4(+)/CD62L(hi) cells express a greater amount of transcripts of GA-binding protein β subunit 1 than those of the spleen. These results suggest that naïve T cells as well as non-T cells and activated/memory T cells from PPs are distinct from their splenic counterparts and thus cause unique immune responses the in intestine., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Peyer's patch (PP) dendritic cells (DCs) have been shown to exhibit a distinct capacity to induce cytokine secretion from CD4(+) T cells compared with DCs in other lymphoid organs such as the spleen (SP). In this study, we investigated whether PP DCs are functionally different from DCs in the SP in their ability to induce Ab production from B cells. Compared with SP DCs, freshly isolated PP DCs induced higher levels of IgA secretion from naive B cells in DC-T cell-B cell coculture system in vitro. The IgA production induced by PP DCs was attenuated by neutralization of IL-6. In addition, the induction of IgA secretion by SP DCs, but not PP DCs, was further enhanced by the addition of exogenous IL-6. Finally, we demonstrated that only PP CD11b(+) DC subset secreted higher levels of IL-6 compared with other DC subsets in the PP and all SP DC populations, and that PP CD11b(+) DC induced naive B cells to produce higher levels of IgA compared with SP CD11b(+) DC. These results suggest a unique role of PP CD11b(+) DCs in enhancing IgA production from B cells via secretion of IL-6.

Aim: The ingestion of Lactiplantibacillus plantarum OLL2712 (OLL2712) cells has been shown to improve glucose metabolism by suppressing chronic inflammation in murine models and clinical studies. This study aimed to clarify the effect of OLL2712 on glycaemic control in healthy adults with prediabetes. Materials and Methods: The study was a randomized, double‐blind, placebo‐controlled, parallel‐group design. Adult participants with prediabetes [n = 148, glycated haemoglobin (HbA1c) range: 5.6%‐6.4%, age range: 20‐64 years] were assigned randomly to placebo or OLL2712 groups (n = 74/group) and administered daily for 12 weeks either conventional yogurt or yogurt containing >5 × 109 heat‐treated OLL2712 cells, respectively. In addition, the participants were followed for 8 weeks after the discontinuation of either yogurt. The primary outcome was the changes in HbA1c levels at weeks 12 and 16 by analysis of covariance. Results: The levels of HbA1c and glycoalbumin decreased significantly in both groups at week 12 in comparison with those at week 0, but only in the OLL2712 group at week 16. HbA1c levels decreased significantly at weeks 12 and 16 in the OLL2712 group in comparison with the placebo group (p =.014 and p =.006, respectively). No significant inter‐ and intragroup differences in HbA1c levels were observed at week 20. Conclusions: The ingestion of OLL2712 prevents the deterioration of glycaemic control and maintains the HbA1c levels within the normal range in adults with prediabetes; yogurt probably exhibits similar effects, which may contribute to reducing the risk of developing type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background Chronic inflammation and insulin resistance are factors that are related to obesity. We have suggested that the administration of heat-treated Lactobacillus plantarum OLL2712 (OLL2712) cells can improve glucose and lipid metabolism by suppressing chronic inflammation in mouse models and a preliminary clinical study. Objective The aim of this study was to investigate whether ingesting OLL2712 cells can reduce body fat accumulation and improve metabolic risk factors, in overweight, healthy adults. Methods This study was a randomized, double-blind, placebo-controlled, parallel-group trial conducted at a single center in Japan. The study participants included 100 overweight (BMI range, ≥25 to <30 kg/m2) adults aged 20–64 y. They were randomly assigned to either the placebo or OLL2712 group (n  = 50 each) and were administered conventional yogurt or yogurt containing >5 × 109 heat-treated OLL2712 cells, respectively, daily for 12 wk. The primary outcome was the 12-wk change in the abdominal fat area, as assessed by computed tomography, and the secondary outcomes were glucose and lipid metabolism-related parameters and chronic inflammation markers, which were analyzed using a linear mixed model. Results The 12-wk change of abdominal fat area (difference: 8.5 cm2; 95% CI: 0.3, 16.6 cm2; P  = 0.040) and fasting plasma glucose (difference: 3.2 mg/dL; 95% CI: 0.8, 5.6 mg/dL; P  = 0.021) were significantly less in the OLL2712 group than the placebo group. The overall trend of serum IL-6 was significantly decreased in the OLL2712 group compared with baseline and the placebo group. Conclusions The ingestion of heat-treated OLL2712 cells reduces body fat accumulation and the deterioration of glycemic control and chronic inflammation, in overweight, healthy adults. We hypothesize that OLL2712 cells may prevent obesity by regulating chronic inflammation. This trial was registered at the University Hospital Medical Information Network Clinical Trials Registry as UMIN000027709. [ABSTRACT FROM AUTHOR]

Abstract: Peyer''s patches (PPs) are potential sites where specific mucosal immune responses and oral tolerance are induced. The unique features of these immune responses are thought to occur in micromilieu and are largely affected by antigen-presenting cells (APCs) such as dendritic cells. In this study, we investigated the cytokine profiles induced by the activation of CD4+ T cells of PPs. PP cells from TCR transgenic mice secreted greater amounts of IL-5 and IL-6 than spleen cells after antigenic stimulation. IL-5 was mainly produced by PP non-T cells, whereas IL-6 was secreted by PP CD4+ cells. PPs contained two major populations including naïve and memory/activated CD4+ cells; both populations secreted IL-6 upon activation. We also found that CD4+/CD62Lhi naïve cells from PPs secreted a greater amount of IL-6 after stimulation than those from the spleen. Furthermore, subtraction and qPCR analyses revealed that PP CD4+/CD62Lhi cells express a greater amount of transcripts of GA-binding protein β subunit 1 than those of the spleen. These results suggest that naïve T cells as well as non-T cells and activated/memory T cells from PPs are distinct from their splenic counterparts and thus cause unique immune responses the in intestine. [Copyright &y& Elsevier]

The ingestion of Lactobacillus plantarum OLL2712 (OLL2712) cells improved glucose metabolism by suppressing chronic inflammation in mouse models and in a preliminary clinical study. We aimed to clarify the effect of OLL2712 on glucose metabolism and chronic inflammation for healthy adults. Prediabetic adults (n = 130, age range: 20–64 years) were randomly assigned to either the placebo or OLL2712 groups (n = 65 each) and were administered conventional yogurt or yogurt containing more than 5 × 109 heat-treated OLL2712 cells, respectively, daily for 12 weeks. Reduced HbA1c levels after 12 weeks of treatment were observed in both groups compared to those at baseline; however, the 12-week reduction of HbA1c levels was significantly greater in the OLL2712 group than in the placebo group. Increased chronic inflammation marker levels and insulin-resistant index (HOMA-IR) occurred in the placebo group but not in the OLL2712 group. Fasting blood glucose (FBG) levels did not change significantly in both groups; however, in subgroup analyses including participants with higher FBG levels, FBG levels were significantly reduced only in the OLL2712 group compared to baseline. These results suggest that OLL2712 cell ingestion can reduce HbA1c levels and can prevent the aggravation of chronic inflammation and insulin resistance. [ABSTRACT FROM AUTHOR]