| Attenuation of islet-specific T cell responses is associated with C-peptide improvement in autoimmune type 2 diabetes patients. | |
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MedLine Citation:
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PMID: 23286943 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The clinical efficacy of peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists in cell-mediated autoimmune diseases results from down-regulation of inflammatory cytokines and autoimmune effector cells. T cell islet autoimmunity has been demonstrated to be common in patients with phenotypic type 2 diabetes mellitus (T2DM) and islet-specific T cells (T(+) ) to be correlated positively with more severe beta cell dysfunction. We hypothesized that the beneficial effects of the PPAR-γ agonist, rosiglitazone, therapy in autoimmune T2DM patients is due, in part, to the immunosuppressive properties on the islet-specific T cell responses. Twenty-six phenotypic T2DM patients positive for T cell islet autoimmunity (T(+) ) were identified and randomized to rosiglitazone (n = 12) or glyburide (n = 14). Beta cell function, islet-specific T cell responses, interleukin (IL)-12 and interferon (IFN)-γ responses and islet autoantibodies were followed for 36 months. Patients treated with rosiglitazone demonstrated significant (P < 0·03) down-regulation of islet-specific T cell responses, although no change in response to tetanus, a significant decrease (P < 0·05) in IFN-γ production and significantly (P < 0·001) increased levels of adiponectin compared to glyburide-treated patients. Glucagon-stimulated beta cell function was observed to improve significantly (P < 0·05) in the rosiglitazone-treated T2DM patients coinciding with the down-regulation of the islet-specific T cell responses. In contrast, beta cell function in the glyburide-treated T2DM patients was observed to drop progressively throughout the study. Our results suggest that down-regulation of islet-specific T cell autoimmunity through anti-inflammatory therapy may help to improve beta cell function in autoimmune phenotypic T2DM patients. |
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Authors:
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B M Brooks-Worrell; J P Palmer |
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Publication Detail:
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Type: Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Clinical and experimental immunology Volume: 171 ISSN: 1365-2249 ISO Abbreviation: Clin. Exp. Immunol. Publication Date: 2013 Feb |
Date Detail:
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Created Date: 2013-01-04 Completed Date: 2013-03-12 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 0057202 Medline TA: Clin Exp Immunol Country: England |
Other Details:
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Languages: eng Pagination: 164-70 Citation Subset: IM |
Copyright Information:
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© 2012 British Society for Immunology. |
Affiliation:
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Department of Medicine, VA Puget Sound Health Care System, Seattle, WA 98108, USA. bbrooks@u.washington.edu |
| Data Bank Information | |
Bank Name/Acc. No.:
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ClinicalTrials.gov/NCT00194896 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Autoantibodies / blood Autoimmunity / drug effects C-Peptide / blood Cells, Cultured Diabetes Mellitus, Type 2 / drug therapy*, immunology Disease Progression Female Follow-Up Studies Glyburide / administration & dosage, adverse effects, pharmacology Humans Hypoglycemic Agents / administration & dosage*, adverse effects, pharmacology Immunosuppression Interferon-gamma / immunology Interleukin-12 / immunology Islets of Langerhans / drug effects, physiology* Male Middle Aged PPAR gamma / agonists* T-Cell Antigen Receptor Specificity / immunology T-Lymphocytes / drug effects, immunology* Thiazolidinediones / administration & dosage*, adverse effects, pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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P01-DK053004/DK/NIDDK NIH HHS; P30-DK017047/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Autoantibodies; 0/C-Peptide; 0/Hypoglycemic Agents; 0/PPAR gamma; 0/Thiazolidinediones; 10238-21-8/Glyburide; 122320-73-4/rosiglitazone; 187348-17-0/Interleukin-12; 82115-62-6/Interferon-gamma |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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