Study on individual immunosuppressive therapy based on peripheral-blood lymphocyte-sensitivity to immunosuppressive drugs and the mechanisms on drug resistance

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This study was carried out to establish pharmacodynamic indices for effective and safety use of immunosuppressive drugs in various immunological disorders. To evaluate individual response to immunosuppressive drugs, we examined lymphocyte suppressive potency of glucocorticoids (prednisolone and methylprednisolone) and immunosuppressants (cyclosporine and tacrolimus) in vitro by use of peripheral-blood lymphocytes obtained from patients with autoimmune disorders including bronchial asthma, rheumatoid arthritis, nephrosis, ulcerative colitis, and renal transplant recipients. We also examined molecular basis for lymphocyte-resistance to immunosuppressive drugs. Lymphocyte sensitivity to immunosuppressants in vitro correlated with clinical efficacy of the drugs in patients of each disease. There may be some different mechanisms for lymphocyte-resistance between these diseases. We concluded that clinical efficacy of immunosuppressants can be predicted by measuring in vitro response of patient's lymphocytes to the drugs. The patients with lymphocytes exhibiting high-sensitivity to the drug might be treated with shorter periods or amounts of the drug, whereas the patients showing lymphocyte resistance to the drug might be refractory to the therapy. The data of in vitro sensitivity to the drugs could be an index for selection of appropriate immunosuppressant to individual patient.