Effect of cyclosporine A on serum tumor necrosis factor alpha in new-onset type I (insulin-dependent) diabetes mellitus.
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)
Burke
G W
GW
Department of Surgery, University of Miami Medical Center, Florida 33136.
Cirocco
R
R
Markou
M
M
Agramonte
R F
RF
Rabinovitch
A
A
Miller
J
J
Skyler
J S
JS
D000704:Analysis of Variance; D002096:C-Peptide / Q000097:blood / Q000378:metabolism; D016572:Cyclosporine / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007515:Islets of Langerhans / Q000187:drug effects / Q000503:physiopathology; D010919:Placebos; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D012016:Reference Values; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism*
D002096:C-Peptide; D016207:Cytokines; D007376:Interleukin-2; D015850:Interleukin-6; D010919:Placebos; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016572:Cyclosporine