15-Deoxyspergualin: a novel immunosuppressive drug with clinical potential.
The studies discussed in this review suggest that DSG is a potent immunosuppressive agent, with at least some of its activity due to its direct effects on macrophages and B cells. The effects of DSG on macrophages include inhibition of IL-1, chemiluminescence, expression of MHC Class I antigen on the surface, and development of MAF. The agent may well interfere with antigen processing and the discovery of its binding to the heat-shock protein 70 may shed some light on this area. The effects of DSG on B lymphocytes include inhibition of surface Ig expression and B cell differentiation. In addition, however, DSG exhibits some effects on both B and T lymphocytes and is markedly active in blocking both the primary and secondary cytotoxic T cell and antibody-producing cell generation. The agent is relatively nontoxic at the doses in which it exerts these marked effects. Thus, an overall assessment of DSG shows that it may provide immune suppression at levels different from those of immunosuppressive agents already available. Advances in human organ transplantation have for the most part occurred stepwise with the introduction of progressively improved techniques of immunosuppression. Tissue-matching, organ preservation, techniques of transplantation, and surgical post-operative care of organ transplant recipients have all improved over the 30 years since organ transplantation began, but have not been the major factors in the improved survival of both patients and grafts seen at the present time. The initial advance in immunosuppression which made the first organ transplants possible was the finding of the immunosuppressive capabilities of azathioprine (Imuran) and the ability to reverse acute rejection crisis with prednisone. Anti-thymocyte or anti-lymphocyte globulin, introduced in 1966, achieved variable results, with some groups reporting excellent patient and graft survival using this agent. Others using different variations of this drug showed no improvement in results. By the mid-1970s, transplant results had improved at a number of units, with graft survivals of kidney and heart recipients in the 70 percent range at 1 to 2 years. No major progress was reported in most units, however, until the introduction in 1978 of cyclosporine. A major effect of cyclosporine was to create a universal improvement in graft survival in all units surveyed around the world with a 70 to 75 percent one-year cadaver kidney graft survival, representing the basic standard for clinical results.(ABSTRACT TRUNCATED AT 400 WORDS)
Thomas
F T
FT
Department of Surgery, University Medical Center-UMC, Greenville, North Carolina 27834.
Tepper
M A
MA
Thomas
J M
JM
Haisch
C E
CE
D000818:Animals; D001682:Biological Availability; D006085:Graft Survival / Q000187:drug effects; D006146:Guanidines / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D006801:Humans; D007109:Immunity / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*
D006146:Guanidines; D007166:Immunosuppressive Agents; C037258:gusperimus