Effect of cyclosporin on interleukin 2-related T-lymphocyte parameters in IDDM patients.
Seventy patients aged 15-40 yr with recent-onset insulin-dependent diabetes mellitus (IDDM) were entered into a double-blind trial, in which they were randomly assigned to either cyclosporin (7.5 mg.kg-1.day-1) or to placebo and were monitored for 1 yr for various phenotypic and functional parameters of T-lymphocyte-mediated immunity. Before treatment, the proportions of total T-lymphocytes (CD3+) and helper-inducer T-lymphocytes (CD4+) were normal, whereas significantly decreased values of suppressor/cytotoxic T-lymphocytes (CD8+), as compared with normal controls, were found in 31% of the patients. The interleukin 2 (IL-2)-receptor expression was significantly increased in IDDM patients compared with control subjects, although the single values were low: patients, 2.02 +/- 0.41%; controls, 0.88 +/- 0.25% (means +/- SE). Circulating levels of soluble IL-2 receptor were also significantly increased in IDDM patients compared with controls: patients, 372.3 +/- 25.4 U/ml; controls, 235.5 +/- 29.3 U/ml (means +/- SE). However, no major abnormalities were found in mitogen (phytohemagglutinin)-induced IL-2 production, cell proliferation, or IL-2-receptor expression. After 6 mo of cyclosporin treatment, no major modifications of any of the parameters analyzed were noted, even in patients who had cyclosporin blood trough levels greater than 300 ng/ml, i.e., the threshold value associated with clinical efficacy. One explanation for the absence of a major effect of cyclosporin, in contrast with its demonstrated clinical effectiveness, is the reversibility of its activity. Our results preclude the use of the described tests to reliably monitor IDDM patients undergoing immunosuppressive therapy.
Chatenoud
L
L
Immunology Clinic, Necker Hospital, Paris, France.
Feutren
G
G
Nelson
D L
DL
Boitard
C
C
Bach
J F
JF
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal; D002986:Clinical Trials as Topic; D003524:Cyclosporins / Q000494:pharmacology / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000628:therapy; D004311:Double-Blind Method; D005455:Fluorescent Antibody Technique; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000096:biosynthesis*; D008137:Longitudinal Studies; D008213:Lymphocyte Activation / Q000187:drug effects; D015375:Receptors, Interleukin-2 / Q000032:analysis; D012016:Reference Values; D013601:T-Lymphocytes / Q000145:classification / Q000187:drug effects / Q000276:immunology*
D000911:Antibodies, Monoclonal; D003524:Cyclosporins; D007376:Interleukin-2; D015375:Receptors, Interleukin-2