Immunosuppressants: Cellular and molecular mechanisms of action

被引:113
作者
Suthanthiran, M
Morris, RE
Strom, TB
机构
[1] CORNELL MED CTR,NEW YORK HOSP,DEPT MED,DIV NEPHROL,NEW YORK,NY
[2] CORNELL MED CTR,NEW YORK HOSP,ROGOSIN INST,DEPT TRANSPLANTAT MED & EXTRACORPOREAL THERAPY,NEW YORK,NY
[3] STANFORD UNIV,MED CTR,DEPT CARDIOTHORAC SURG,LAB TRANSPLANTAT IMMUNOL,STANFORD,CA 94305
[4] HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DIV IMMUNOL,BOSTON,MA
关键词
immunosuppressants; antiallograft response; cytokines; monoclonal antibodies;
D O I
10.1016/S0272-6386(96)90297-8
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
The basic immunosuppressive protocol used in most transplant centers involves the use of multiple drugs, each directed at a discrete site in the T-cell activation cascade and each with distinct side effects. Cyclosporine, azathioprine, corticosteroids, FK506 (tacrolimus), and RS61443 (mycophenolate mofetil) have been approved by the Food and Drug Administration, and the clinical efficacy of rapamycin (sirolimus), mizoribine, 15-deoxyspergualin, and leflunomide is being explored, Based on their primary site of action, the immunosuppressants can be classified as inhibitors of transcription (cyclosporine, tacrolimus), inhibitors of nucleotide synthesis (azathioprine, mycophenolate mofetil, mizoribine, leflunomide), inhibitors of growth factor signal transduction (sirolimus, leflunomide), and inhibitors of differentiation (15-deoxyspergualin). Polyclonal antilymphocyte antibodies, monoclonal antibodies directed at the T-cell antigen receptor complex (OKT3, TIOB9), and monoclonal antibodies directed at additional cell surface antigens, including interleukin-2 receptor alpha, afford cell-specific regulation of the immune response and are being used in the clinical setting as induction therapy and/or antirejection drugs. Clearly, the transplant clinician now has a greater choice in the selection and application of immunosuppressants in the clinic for the fine regulation of the antiallograft repertory. The prevailing paradigm regarding the mechanisms of action of immunosuppressants is that they all function to prevent allograft rejection by preventing/inhibiting cell activation, cytokine production, differentiation, and/or proliferation. One hypothesis, albeit provocative, is that some of the immunosuppressants might function by stimulating the expression of immunosuppressive molecules and/or cells. (C) 1996 by the National Kidney Foundation, Inc.
引用
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页码:159 / 172
页数:14
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