Abstract
This article was explained the mechanisms of action and the administration method of immunosuppressive drugs currently used in Japan. The available drugs are classified into the following categories; 1) the immunosuppressants which inhibit cytokine production, 2) anti-synthesis drugs of nucleic acids, 3) steroidhormons, 4) biological products, and 5) others. Cyclosporine and tacrolimus are included in Category 1), and they have similar action mechanisms to inhibit IL-2 release from helper T cells. In Category 2), we have azathiopurine and mizoribin. The former inhibits purine biosynthesis not only in lymphocytes but also other organ cells, resulting in severe side effects. However, the latter inhibits de novo pathway of purine synthesis, which induces lymphocyte-specific inhibition but not affects other organ cells. Thus, mizoribin exhibits a low toxicity in the recipients, although its immunosuppressive activity is lower than other drugs. Glucocorticoids (Prednisolone and methylprednisolone) are usually used as the drugs included in Category 3), and have variety of action modes, such as inhibition of IL-1, IL-2, IFN-gamma, and anti-inflammatory effect, as well as induction of lymphocyte apoptosis at a high dose. Category 4) includes anti-lymphocyte policlonal antibodies (ALG) and monoclonal antibody (OKT-3). Gusperimus hydrochloride, or deoxyspergualin, classified into Category 5), inhibits premature CTL into mature cells. The immunosuppressive regimens after grafting are generally performed by combination of various drugs; i. e. cyclosporine+steroid+azathiopurine or mizoribin, or tacrolimus+steroid+/-azathiopurine or mizoribin. In addition, methylprednisolone at a bolus dose, gusperimus hydrochloride, or OKT-3 is administered for the treatment of acute rejection.
