FK-506 - A NOVEL IMMUNOSUPPRESSANT

In this brief review, we outline the properties of the new macrolide immunosuppressant FK-506. This selective anti-T cell agent has a similar mode of action to cyclospirin A (CSA). It is, however, more powerful, has the capacity (unlike CSA) to reverse liver allograft rejection and appears to have a higher therapeutic index than CSA in patients receiving organ transplants. Preliminary data suggest that renal function is better in recipients of liver transplants given FK-506 as primary therapy compared with those given CSA. In addition, evidence has been presented that FK-506-treated patients have shorter hospital stay than those receiving treatment with CSA. Other factors require to be taken into account, but it may be that it will prove less expensive in the future to treat patients with FK-506 than with CSA. The potential of FK-506 for the control of autoimmune diseases has been demonstrated in rodent models of rheumatoid arthritis, type I diabetes, posterior uveitis, allergic encephalomyelitis and glomerulonephritis. In the clinical field. FK-506 has been used in two cases of nephrotic syndrome resulting from glomerulonephritis; there was improvement in proteinuria and no decline in renal function. Studies to date have been restricted to one clinical centre although many hundreds of organ graft recipients have been studied. Both longer term and multicentre investigations are urgently required, but it appears that FK-506 may offer considerable potential as an immunotherapeutic agent.