Effects of cyclosporin A upon humoral and cellular immune parameters in insulin-dependent diabetes mellitus type I: a long-term follow-up study.

Patients who had been included in a randomized double-blind placebo-controlled trial on the efficacy of cyclosporin A (CyA) in producing remissions in insulin-dependent diabetes mellitus (IDDM) type I were investigated for humoral and cellular immunologic parameters. Whereas metabolic derangement before the initiation of insulin treatment led to small but significant decreases in the percentage of CD4-positive lymphocytes as well as of the activity of natural killer (NK) cells and antibody-dependent cellular cytotoxicity (ADCC), the administration of CyA did not influence any of the immunologic parameters tested, which included proliferative lymphocyte responses to mitogens and alloantigens and serum concentrations of immunoglobulins G, A and M. Thus NK cell activity, ADCC as well as the percentage of CD4-positive lymphocytes returned to normal levels in parallel with the normalization of glycosylated haemoglobin (HbAlc), but were not further influenced in their course by the administration of CyA, as compared with patients receiving placebo. Interferon-induced augmentation of NK cell activity did not differ between patients with IDDM on placebo and those under CyA therapy. All other investigated parameters also remained unchanged during the time of CyA therapy. We conclude that metabolic derangement leads to a reversible disturbance of certain cellular immune functions, but their normalization achieved by insulin treatment and their further course remains uninfluenced by the administration of CyA.

[Results of cyclosporin A therapy in the early phase of type I diabetes mellitus]. / Ergebnisse der Cyclosporin-A-Therapie in der Frühphase des Typ-I-Diabetes mellitus*.

A number of findings concerning the pathogenesis of insulin-dependent diabetes mellitus have shown that an autoimmune process is responsible for the destruction of the beta-cell mass, and that a major part of this process has already occurred during the prediabetic phase of the disease. Various immunosuppressive intervention trials have, thus, recently been performed. Remission rates of between 30% and 50% in the Canadian cyclosporin A (CyA) pilot study prompted two placebo-controlled double-blind studies applying this medication. In the French CyA trial 122 patients were followed up for 9 months. 37% of those on high-dose CyA (whole blood levels greater than 300 ng/ml) achieved total remission, compared with 16.7% of those on low-dose CyA (blood level less than 300 ng/ml) and 5% of the placebo group. The Canadian-European trial included 188 patients, of whom 42 were treated in the Viennese centre. Diabetes had been diagnosed in these 42 patients not more than 6 weeks previously, and the duration of their symptoms did not exceed 14 weeks. Whole blood CyA levels ranged from 400 to 800 ng/ml. In relation to short duration of symptoms and early commencement of treatment up to 10 times higher total remission rates were found in the CyA group as compared with the placebo group. In both studies similar side effects were seen. Apart from the cosmetic side effects (hypertrichosis, gingival hyperplasia) a decrease of 20% in creatinine clearance and an increase of 20% in plasma creatinine level seemed to be of clinical importance.(ABSTRACT TRUNCATED AT 250 WORDS)