Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Over the last few years, improved knowledge of the immunological mechanisms underlying transplant rejection have resulted in the development of new immunosuppressive agents capable of selectively blocking various steps of the immune response. It is anticipated that these agents will prove useful in the treatment of autoimmune disease and graft-versus-host disease. Neoral is a cyclosporin microemulsion characterized by better and more consistent absorption as compared to the conventional galenic form. Tacrolimus shares with cyclosporin an ability to inhibit calcineurin and may have similar indications. Rapamycin and RAD are two related molecules that inhibit signal transduction by cytokines to T-cells, although they have not yet been proved clinically effective in large studies of solid organ transplant recipients. Mycophenolate mofetil selectively inhibits purine synthesis and lymphocyte proliferation; it is easy to use and has been found effective in a number of autoimmune disorders. Further clinical work is needed to determine the therapeutic indications for each of these new drugs. Elucidation of their mechanisms of action may help to identify drug combinations providing both enhanced efficacy and improved safety.
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PMID:[New immunosuppressive agents]. 1057 3

The 4-aminoquinolines, chloroquine and hydroxychloroquine, can suppress chronic graft-versus-host disease (GVHD) following blood and marrow transplantation (BMT) in mice and humans, respectively. We hypothesized that chloroquine in combination with tacrolimus and the rapamycin derivative SDZ-RAD can synergistically suppress T cell responses and antigen-presenting cell (APC) function in vitro. We used the APC-dependent C57BL/6 anti-BALB.B T cell response and APC-independent anti-CD3epsilon antibody-induced response to evaluate the role of synergism between chloroquine and tacrolimus or SDZ-RAD on each component of a T cell response to minor histocompatibility antigens. We found that chloroquine with tacrolimus had a greater synergistic suppression of APC-dependent compared to the APC-independent T cell responses, with a combination index (CIx) for 50% inhibition by mean effect analysis of 0.16 and 0.50, respectively (a lower number indicates greater suppression). By contrast, chloroquine with SDZ-RAD had a similar CIx between the two responsed 0.50 vs0.45) suggesting only T cell suppression. Synergy between chloroquine and SDZ-RAD involved a direct effect on T cell cytokine production, whereas synergism between chloroquine and tacrolimus was due to an effect on both T cells and APCs. We conclude that the renal-sparing 4-aminoquinolines may be used syneristically with immunosuppressive drugs currently used for BMT.
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PMID:Evaluation for synergistic suppression of T cell responses to minor histocompatibility antigens by chloroquine in combination with tacrolimus and a rapamycin derivative, SDZ-RAD. 1247 84