Ciclosporin-induced immunosuppression in vitro. II. Variation in sensitivity and binding capacity.

The purpose of the present study was to analyse and correlate variations in lymphocyte sensitivity to, and binding of, ciclosporin (CsA) in vitro. Peripheral blood lymphocytes from healthy individuals were harvested over a 5-week period and activated with purified protein derivative (PPD) or alloantigens in the presence or absence of CsA (1 microgram/ml). Sensitivity to CsA was expressed as the ability of the drug to suppress cell proliferation ([3H]thymidine incorporation) and high-affinity interleukin-2 receptor (IL-2R) expression. Binding capacity was tested in a [3H]CsA binding assay. A significant variability in both sensitivity and binding capacity was recorded between individuals (P less than 0.001). There was no correlation between high sensitivity and high binding capacity. The intraindividual day-to-day variability did not differ significantly from the experimental (intra- and interassay) variability. The CsA-induced suppression of high-affinity IL-2R expression varied between 57.1 and 98.9%, while suppression of [3H]thymidine incorporation varied between 81.0 and 97.4%. Specific binding of 10 nM [3H]CsA at 37 degrees C varied between 5.4 and 10.7%.