Effect of cyclosporine a on serum tumor necrosis factor α in new-onset type I (insulin-dependent) diabetes mellitus

George W Burke, Robert Cirocco, Michael Markou, Robert F. Agramonte, Alexander Rabinovitch, Joshua Miller, Jay S Skyler

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Because the etiology of insulin-dependent diabetes mellitus (IDDM) is thought to be autoimmune, several clinical trials have utilized immunosuppression to treat newly diagnosed diabetic patients. In the University of Miami trial, cyclosporine A (CyA) was used to treat one group (n = 10), while the other received placebo (n = 13). During the 1-year study, islet β-cell function was better preserved in the CyA group compared to the placebo group, based on the response (C-peptide production) to a physiologic stimulus (meal challenge). Specifically, when measured by regression analysis, the slope defining the rate of decline of β-cell function was significantly lower for the CyA-treated group (p < 0.05). Cytokine levels were analyzed retrospectively from frozen (-70°C) stored sera from both groups. At time 0, tumor necrosis factor α (TNFα) levels were similar in the Cya (40.1 ± 14.2 pg/mL) and placebo group (38.5 ± 12.1 pg/mL) of IDDM subjects (normal 32.0 ± 5.0 pg/mL). At 1 month, the level of TNFα in the CyA group was significantly lower than that observed in the placebo group (22.3 ± 7.2 versus 53.3 ± 8.9 pg/mL (P < .05). TNFα levels subsequently fell in the placebo group and were not significantly different between placebo and CyA groups. Soluble interleukin 2 receptor (IL-2R) levels in IDDM patients were significantly higher than in normal subjects at diagnosis of IDDM. For the next 6 months, these levels fell consistently in both the CyA and placebo groups. Serum interleukin 2 (IL-2) levels in IDDM subjects were higher than normal at the time of diagnosis of IDDM, but were not statistically different between groups over the 6-month period. Serum levels of interleukin 6 (IL-6) and γ interferon (γIFN) were similar in IDDM and normal subjects, and not different over 6 months in the CyA and placebo groups of IDDM subjects. TNFα and other cytokines, including IL-1, IL-6, and γIFN have been implicated as possible mediators of islet β-cell destruction in IDDM. In this study, serum TNFα levels fell after 1 month of CyA treatment in newly diagnosed IDDM patients. The effect of CyA to preserve islet β-cell function better in these patients may be related to decreased production of TNFα.

Original languageEnglish
Pages (from-to)40-44
Number of pages5
JournalJournal of Diabetes and its Complications
Volume8
Issue number1
DOIs
StatePublished - Jan 1 1994

Fingerprint

Type 1 Diabetes Mellitus
Cyclosporine
Tumor Necrosis Factor-alpha
Placebos
Serum
Islets of Langerhans
Interferons
Interleukin-6
Cytokines
C-Peptide
Interleukin-2 Receptors
Interleukin-1
Immunosuppression
Interleukin-2
Meals
Regression Analysis
Clinical Trials

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Effect of cyclosporine a on serum tumor necrosis factor α in new-onset type I (insulin-dependent) diabetes mellitus. / Burke, George W; Cirocco, Robert; Markou, Michael; Agramonte, Robert F.; Rabinovitch, Alexander; Miller, Joshua; Skyler, Jay S.

In: Journal of Diabetes and its Complications, Vol. 8, No. 1, 01.01.1994, p. 40-44.

Research output: Contribution to journalArticle

Burke, George W ; Cirocco, Robert ; Markou, Michael ; Agramonte, Robert F. ; Rabinovitch, Alexander ; Miller, Joshua ; Skyler, Jay S. / Effect of cyclosporine a on serum tumor necrosis factor α in new-onset type I (insulin-dependent) diabetes mellitus. In: Journal of Diabetes and its Complications. 1994 ; Vol. 8, No. 1. pp. 40-44.
@article{9adfb1f783464ec2a2c951e740f43072,
title = "Effect of cyclosporine a on serum tumor necrosis factor α in new-onset type I (insulin-dependent) diabetes mellitus",
abstract = "Because the etiology of insulin-dependent diabetes mellitus (IDDM) is thought to be autoimmune, several clinical trials have utilized immunosuppression to treat newly diagnosed diabetic patients. In the University of Miami trial, cyclosporine A (CyA) was used to treat one group (n = 10), while the other received placebo (n = 13). During the 1-year study, islet β-cell function was better preserved in the CyA group compared to the placebo group, based on the response (C-peptide production) to a physiologic stimulus (meal challenge). Specifically, when measured by regression analysis, the slope defining the rate of decline of β-cell function was significantly lower for the CyA-treated group (p < 0.05). Cytokine levels were analyzed retrospectively from frozen (-70°C) stored sera from both groups. At time 0, tumor necrosis factor α (TNFα) levels were similar in the Cya (40.1 ± 14.2 pg/mL) and placebo group (38.5 ± 12.1 pg/mL) of IDDM subjects (normal 32.0 ± 5.0 pg/mL). At 1 month, the level of TNFα in the CyA group was significantly lower than that observed in the placebo group (22.3 ± 7.2 versus 53.3 ± 8.9 pg/mL (P < .05). TNFα levels subsequently fell in the placebo group and were not significantly different between placebo and CyA groups. Soluble interleukin 2 receptor (IL-2R) levels in IDDM patients were significantly higher than in normal subjects at diagnosis of IDDM. For the next 6 months, these levels fell consistently in both the CyA and placebo groups. Serum interleukin 2 (IL-2) levels in IDDM subjects were higher than normal at the time of diagnosis of IDDM, but were not statistically different between groups over the 6-month period. Serum levels of interleukin 6 (IL-6) and γ interferon (γIFN) were similar in IDDM and normal subjects, and not different over 6 months in the CyA and placebo groups of IDDM subjects. TNFα and other cytokines, including IL-1, IL-6, and γIFN have been implicated as possible mediators of islet β-cell destruction in IDDM. In this study, serum TNFα levels fell after 1 month of CyA treatment in newly diagnosed IDDM patients. The effect of CyA to preserve islet β-cell function better in these patients may be related to decreased production of TNFα.",
author = "Burke, {George W} and Robert Cirocco and Michael Markou and Agramonte, {Robert F.} and Alexander Rabinovitch and Joshua Miller and Skyler, {Jay S}",
year = "1994",
month = "1",
day = "1",
doi = "10.1016/1056-8727(94)90009-4",
language = "English",
volume = "8",
pages = "40--44",
journal = "Journal of Diabetes and its Complications",
issn = "1056-8727",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Effect of cyclosporine a on serum tumor necrosis factor α in new-onset type I (insulin-dependent) diabetes mellitus

AU - Burke, George W

AU - Cirocco, Robert

AU - Markou, Michael

AU - Agramonte, Robert F.

AU - Rabinovitch, Alexander

AU - Miller, Joshua

AU - Skyler, Jay S

PY - 1994/1/1

Y1 - 1994/1/1

N2 - Because the etiology of insulin-dependent diabetes mellitus (IDDM) is thought to be autoimmune, several clinical trials have utilized immunosuppression to treat newly diagnosed diabetic patients. In the University of Miami trial, cyclosporine A (CyA) was used to treat one group (n = 10), while the other received placebo (n = 13). During the 1-year study, islet β-cell function was better preserved in the CyA group compared to the placebo group, based on the response (C-peptide production) to a physiologic stimulus (meal challenge). Specifically, when measured by regression analysis, the slope defining the rate of decline of β-cell function was significantly lower for the CyA-treated group (p < 0.05). Cytokine levels were analyzed retrospectively from frozen (-70°C) stored sera from both groups. At time 0, tumor necrosis factor α (TNFα) levels were similar in the Cya (40.1 ± 14.2 pg/mL) and placebo group (38.5 ± 12.1 pg/mL) of IDDM subjects (normal 32.0 ± 5.0 pg/mL). At 1 month, the level of TNFα in the CyA group was significantly lower than that observed in the placebo group (22.3 ± 7.2 versus 53.3 ± 8.9 pg/mL (P < .05). TNFα levels subsequently fell in the placebo group and were not significantly different between placebo and CyA groups. Soluble interleukin 2 receptor (IL-2R) levels in IDDM patients were significantly higher than in normal subjects at diagnosis of IDDM. For the next 6 months, these levels fell consistently in both the CyA and placebo groups. Serum interleukin 2 (IL-2) levels in IDDM subjects were higher than normal at the time of diagnosis of IDDM, but were not statistically different between groups over the 6-month period. Serum levels of interleukin 6 (IL-6) and γ interferon (γIFN) were similar in IDDM and normal subjects, and not different over 6 months in the CyA and placebo groups of IDDM subjects. TNFα and other cytokines, including IL-1, IL-6, and γIFN have been implicated as possible mediators of islet β-cell destruction in IDDM. In this study, serum TNFα levels fell after 1 month of CyA treatment in newly diagnosed IDDM patients. The effect of CyA to preserve islet β-cell function better in these patients may be related to decreased production of TNFα.

AB - Because the etiology of insulin-dependent diabetes mellitus (IDDM) is thought to be autoimmune, several clinical trials have utilized immunosuppression to treat newly diagnosed diabetic patients. In the University of Miami trial, cyclosporine A (CyA) was used to treat one group (n = 10), while the other received placebo (n = 13). During the 1-year study, islet β-cell function was better preserved in the CyA group compared to the placebo group, based on the response (C-peptide production) to a physiologic stimulus (meal challenge). Specifically, when measured by regression analysis, the slope defining the rate of decline of β-cell function was significantly lower for the CyA-treated group (p < 0.05). Cytokine levels were analyzed retrospectively from frozen (-70°C) stored sera from both groups. At time 0, tumor necrosis factor α (TNFα) levels were similar in the Cya (40.1 ± 14.2 pg/mL) and placebo group (38.5 ± 12.1 pg/mL) of IDDM subjects (normal 32.0 ± 5.0 pg/mL). At 1 month, the level of TNFα in the CyA group was significantly lower than that observed in the placebo group (22.3 ± 7.2 versus 53.3 ± 8.9 pg/mL (P < .05). TNFα levels subsequently fell in the placebo group and were not significantly different between placebo and CyA groups. Soluble interleukin 2 receptor (IL-2R) levels in IDDM patients were significantly higher than in normal subjects at diagnosis of IDDM. For the next 6 months, these levels fell consistently in both the CyA and placebo groups. Serum interleukin 2 (IL-2) levels in IDDM subjects were higher than normal at the time of diagnosis of IDDM, but were not statistically different between groups over the 6-month period. Serum levels of interleukin 6 (IL-6) and γ interferon (γIFN) were similar in IDDM and normal subjects, and not different over 6 months in the CyA and placebo groups of IDDM subjects. TNFα and other cytokines, including IL-1, IL-6, and γIFN have been implicated as possible mediators of islet β-cell destruction in IDDM. In this study, serum TNFα levels fell after 1 month of CyA treatment in newly diagnosed IDDM patients. The effect of CyA to preserve islet β-cell function better in these patients may be related to decreased production of TNFα.

UR - http://www.scopus.com/inward/record.url?scp=0028117122&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028117122&partnerID=8YFLogxK

U2 - 10.1016/1056-8727(94)90009-4

DO - 10.1016/1056-8727(94)90009-4

M3 - Article

C2 - 8167386

AN - SCOPUS:0028117122

VL - 8

SP - 40

EP - 44

JO - Journal of Diabetes and its Complications

JF - Journal of Diabetes and its Complications

SN - 1056-8727

IS - 1

ER -