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TLR-induced secretion of novel cytokine IL-27 is defective in newly diagnosed type-2 diabetic subjects.

ABSTRACT: Toll-like receptors (TLRs), the innate immune receptors, act as sentinels bridging both innate and adaptive arms of immunity. In the present study, we estimated TLR-induced secretion of IL-27, IL-12, IL-23, IL-8, IP-10, IL-17, IL-6 and TNF-? (by ELISA) and expression of Human Leukocyte Antigen- (Human Leukocyte Antigen - antigen D Related (HLA-DR), CD69, CD80 (also known asB7-1) (by flowcytometry) and Activating Transcription Factor 3(ATF3) (by qRT-PCR) in whole blood cultures of control and type-2 diabetic (both newly diagnosed/NDD and known/KDM) subjects. TLR-induced secretion of IL-27 was significantly reduced in the NDD group compared to the control (Normal Glucose Tolerance (NGT)) and KDM groups. On the other hand, the expression of CD80 was significantly upregulated in both the monocytes and B cells in KDM group. This was associated with increased T cell activation (CD3+CD69+HLA-DR+) with increased IL-17 and reduced TNF-? secretion in this group. Impaired TLR-induced IL-27 secretion and augmented expression of antigen presentation molecules result in chronic T cell activation which may fuel T cell-mediated inflammation in type-2 diabetes.

SUBMITTER: Madhumitha H

PROVIDER: S-EPMC6367208 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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TLR-induced secretion of novel cytokine IL-27 is defective in newly diagnosed type-2 diabetic subjects.

Madhumitha Haridoss H Mohan Viswanathan V Babu Subash S Aravindhan Vivekanandhan V

Cytokine 20171003

Toll-like receptors (TLRs), the innate immune receptors, act as sentinels bridging both innate and adaptive arms of immunity. In the present study, we estimated TLR-induced secretion of IL-27, IL-12, IL-23, IL-8, IP-10, IL-17, IL-6 and TNF-α (by ELISA) and expression of Human Leukocyte Antigen- (Human Leukocyte Antigen - antigen D Related (HLA-DR), CD69, CD80 (also known asB7-1) (by flowcytometry) and Activating Transcription Factor 3(ATF3) (by qRT-PCR) in whole blood cultures of control and typ ...[more]

PMID: 28985996

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Project description:ObjectiveAnti-vascular endothelial growth factor therapies have revolutionized the treatment of clinically significant diabetic macular edema (CSDME); yet these agents are expensive, and whether they are cost-effective is unclear. The purpose of this study is to determine the most cost-effective treatment option for patients with newly diagnosed CSDME: focal laser photocoagulation alone (L), focal laser plus intravitreal ranibizumab (L+R), focal laser plus intravitreal bevacizumab (L+B), or focal laser plus intravitreal triamcinolone (L+T) injections.DesignCost-effectiveness analysis.ParticipantsHypothetical cohort of 57-year-old patients with newly diagnosed CSDME.MethodsBy using a Markov model with a 25-year time horizon, we compared the incremental cost-effectiveness of treating patients with newly diagnosed CSDME using L, L+R, L+B, or L+T. Data came from the DRCRnet randomized controlled trial, the Medicare fee schedule, and the medical literature.Main outcome measuresCosts, quality-adjusted life years (QALYs), and incremental costs per QALY gained.ResultsCompared with L, the incremental cost-effectiveness of L+R and L+B was $89903/QALY and $11138/QALY, respectively. L+T was dominated by L. A probabilistic sensitivity analysis demonstrated that, at a willingness to pay (WTP) of $50000/QALY, L was approximately 70% likely to be the preferred therapy over L+R and L+T. However, at a WTP of $100000/QALY, more than 90% of the time, L+R therapy was the preferred therapy compared with L and L+T. In the probabilistic sensitivity analysis, L+B was found to be the preferred therapy over L and L+T for any WTP value >$10000/QALY. Sensitivity analyses revealed that the annual risk of cerebrovascular accident would have to be at least 1.5% higher with L+B than with L+R for L+R to be the preferred treatment. In another sensitivity analysis, if patients require <8 injections per year over the remainder of the 25-year time horizon, L+B would cost <$100000/QALY, whereas L+R would be cost-effective at a WTP of $100000/QALY if patients require fewer than 0.45 injections per year after year 2.ConclusionsWith bevacizumab and ranibizumab assumed to have equivalent effectiveness and similar safety profiles when used in the management of CSDME, bevacizumab therapy confers the greatest value among the different treatment options for CSDME.Financial disclosure(s)The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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Dataset Information

TLR-induced secretion of novel cytokine IL-27 is defective in newly diagnosed type-2 diabetic subjects.

Publications

TLR-induced secretion of novel cytokine IL-27 is defective in newly diagnosed type-2 diabetic subjects.

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