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The effects of four immunosuppressive agents on the in vitro blastogenesis of peripheral blood lymphocytes activated by concanavalin A have been studied using cells from 26 healthy subjects, 34 patients with chronic renal failure (CRF) and 30 kidney transplant recipients. Differences in lymphocyte sensitivity to prednisolone between the healthy subjects and the CRF patients were statistically significant (P less than 0.0002), with impaired sensitivity in CRF. Impaired lymphocyte sensitivity occurred in 3.8% and 52.9% of the healthy and CRF subjects, respectively. Lymphocyte sensitivity to prednisolone, both preoperatively and 3 months post-operatively, was strongly correlated with early allograft rejection during co-administration of prednisolone with cyclosporin or azathioprine. Lymphocyte sensitivity to cyclosporin, azathioprine, and mizoribine in CRF was not significantly less than that in healthy subjects. Since the pharmacokinetics of prednisolone are little altered in renal transplantation, it is concluded that lymphocyte sensitivity specific to prednisolone may be a pharmacodynamic marker characteristic of successful graft survival in patients with histo-incompatibility and/or drug resistance.

The ability of cultured peripheral-blood mononuclear cells (PBMC) to release interleukin-1 alpha and beta (IL-1 alpha, IL-1 beta) in response to concanavalin A (con A) was investigated in patients with chronic renal failure (CRF) and in renal transplant recipients. Mean IL-1 alpha level released by PBMC of healthy subjects (n = 42), CRF patients (n = 42), or transplants 2 months after operation (n = 69) was 152 +/- 103, 110 +/- 80, or 154 +/- 87 pg/5 x 10(5) cells/ml culture, respectively. IL-1 alpha release from PBMC of recipients 2 months after renal transplantation was significantly higher than that of CRF patients (p less than 0.05). Mean IL-1 beta level released by PBMC of healthy subjects (n = 34), CRF (n = 30), or transplants (n = 55) was 223 +/- 159, 135 +/- 129, or 276 +/- 155 pg/5 x 10(5) cells, respectively. Similar to IL-1 alpha, the level in CRF was significantly lower than that in healthy subjects (p less than 0.05). A time course study indicated that the ability of PBMC from transplants to release IL-1 alpha and beta promptly decreased following the operation, possibly owing to prednisolone and ciclosporin immunosuppressive therapy. However, after maintaining a low level for 2-3 weeks, IL-1 release from PBMC gradually increased thereafter. The results were consistent with known characteristics of decreased immunity in CRF states, and further suggested that the decreased ability of PBMC to release IL-1 alpha and beta in response to con A in CRF patients is recovered 2 months after renal transplantation.