Circulating levels of cyclosporin A in inflammatory bowel disease: relationships with lymphocyte inhibition and the age of patients.

OBJECTIVE

To determine in the same blood sample the concentrations of cyclosporin A (CsA) and the degree of CsA-induced lymphocyte inhibition; to establish a relationship between these parameters; and to investigate the factor(s) influencing such a putative relationship.

METHODS

Ten patients with a diagnosis of Crohn's disease (n=7) or ulcerative colitis (n=3) were enrolled in the study. The patients, who had never been immunosuppressed, were treated with microemulsion CsA twice daily by the oral route; at steady-state, blood samples were collected 0, 0.5, 1, 2, 3, 5, 7 and 12 h after the morning dose. CsA blood levels were measured by means of radioimmunoassay. The percentages of lymphocytes during the S-phase were assessed by flow-cytometry on the same blood specimens, only for samples collected at 0 h and 2 h.

RESULTS

An inverse relationship emerged between CsA blood concentrations and the percentage of lymphocytes during the S-phase: the latter was maximal before the beginning of treatment and minimal in association with peak CsA levels. Furthermore, a highly significant correlation was found between trough CsA levels and the age of the patient, since the percentage of inhibited lymphocytes increases with age.