Immunity during cyclosporine therapy.

Cyclosporine is not cytotoxic but it inhibits the production of immunologic memory-building growth factors by CD4+ T lymphocytes. It also may have inhibitory effects on the effector phase of certain immune reactions. These inhibitory effects are largely reversible and when treatment is stopped, the immune competence of cyclosporine-treated patients returns to normal. In contrast, conventional cytotoxic immunosuppressive agents tend to exterminate the lymphocyte clones that are activated during therapy, and such clonal deletions may cause permanent loss of immunologic memory to those antigens because T lymphocytes are not readily restored in adults with involuted thymus. Most transplant patients have received cyclosporine in combination with various other immunosuppressive agents, and reports suggest that a combination of this drug and conventional immunosuppressive agents may be associated with increased early appearance of non-Hodgkin's lymphoma and, possibly, endocrine-related tumors. An increase in cancers has not been observed in patients treated with cyclosporine alone for such conditions as psoriasis and autoimmune diseases. Treatment of adults with cytotoxic immunosuppressive drugs may permanently delete T-lymphocyte clones that are required for control of latent oncogenic viruses or certain malignant cells. Because of this, when such patients are treated with cyclosporine, further suppression of T-cell function combined with impairment of cytokine-mediated stimulation of natural killer cells and cytotoxic macrophages may facilitate tumor growth. Consequently, it is predicted that if cyclosporine monotherapy is associated with an increased incidence of tumors, it would primarily affect psoriasis patients who are treated with cyclosporine after PUVA or methotrexate therapy. Eventually, comparison of cancer incidence in different categories of patients should resolve this issue.