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

J Diabetes Complications. 1994 Jan-Mar;8(1):40-4. doi: 10.1016/1056-8727(94)90009-4.

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 beta-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 beta-cell function was significantly lower for the CyA-treated group (p < 0.05). Cytokine levels were analyzed retrospectively from frozen (-70 degrees C) stored sera from both groups. At time 0, tumor necrosis factor alpha (TNF alpha) 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 TNF alpha 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). TNF alpha 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analysis of Variance
  • C-Peptide / blood
  • C-Peptide / metabolism
  • Cyclosporine / therapeutic use*
  • Cytokines / blood*
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / physiopathology
  • Double-Blind Method
  • Humans
  • Interferon-gamma / blood
  • Interleukin-2 / blood
  • Interleukin-6 / blood
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / physiopathology
  • Placebos
  • Receptors, Interleukin-2 / metabolism
  • Reference Values
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • C-Peptide
  • Cytokines
  • Interleukin-2
  • Interleukin-6
  • Placebos
  • Receptors, Interleukin-2
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Cyclosporine