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At least 451 records · Page 25Linked to original sources
PubMed1987

S. aureus-induced B cell proliferation as a model for studying the effectiveness of immunosuppressive agents.

S. aureus Cowan-induced proliferation of human T lymphocytes was used as a model for evaluating the activity of most common immunosuppressants (steroids, cyclosporine and azathioprine). Methylprednisolone was found to be the most efficient steroid, followed by hydrocortisone and dexamethasone. Cyclosporine (CsA) was a potent inhibitor acting early after B cell stimulation. Azathioprine was found to have low effect on B cell activation.

Azathioprine↗
PubMed1997

Immunosuppressive agents in clinical trials in transplantation.

Many new agents are in or near clinical trials in organ transplantation. The small molecule antibioticlike drugs are inhibitors of key enzymes in T-cell signal transduction (calcineurin target of rapamycin [TOR], and inosine monophosphate dehydrogenase). Calcineurin inhibitors include cyclosporine microemulsion formulation generic cyclosporine preparations, and tacrolimus. Rapamycin (also known as sirolimus) acts on target of rapamycin to abrogate signals necessary for clonal expansion and is now in phase III. Recent trials of mycophenolate mofetil, an inhibitor of inosine monophosphate dehydrogenase, have shown that it reduces acute renal graft rejection when used with steroids and cyclosporine. New protein reagents in trials include polyclonal antilymphocyte antibodies, mouse monoclonal antibodies, "humanized" mouse monoclonals, and engineered proteins based on naturally occurring signalling molecules. Humanized antibodies against the interleukin-2 receptor are promising because humanized antibodies should combine low toxicity with the potential for long-term use. Engineered human proteins designed to block costimulatory molecules on antigen-presenting cells could have similar potential for low toxicity and extended use. These agents are designed to reduce acute rejection and the toxicity of the existing drugs and eventually improve long-term patient and graft survival. Organ transplant practice will probably change considerably as these agents become available.

Clinical Trials as Topic↗
PubMed1998

Preclinical evaluation of a new immunosuppressive agent, FTY720.

FTY720 is a synthetic analog of a fungal metabolite that shows potent immunosuppressive activity in vitro and in vivo with little apparent toxicity. The drug displays marked synergistic effects in vivo with CsA and/or rapamycin. Therefore, this drug may improve the therapeutic window of agents that target cytokine synthesis or signal transduction. Because of these promising findings, the agent is likely to be tested in humans as an adjunct to clinical immunosuppressive regimens.

Animals↗
PubMed1998

Treatment of severe aplastic anemia with an immunosuppressive agent plus recombinant human granulocyte-macrophage colony-stimulating factor and erythropoietin.

To evaluate the therapeutic potential of hematopoietic growth factors (HGFs) during immunosuppressive treatment (IST) of severe aplastic anemia (SAA), 38 patients with newly diagnosed SAA received IST alone (group I), or IST plus recombinant human erythropoietin and granulocyte-macrophage colony-stimulating factor (rhEPO + rhGM-CSF) (group II). Eleven patients in each group received antilymphocyte globulin (ALG) for IST, and eight patients in each group received cyclosporine (CSA). Complete remission rates at one year were 26% and 74% for group I and group II patients, respectively. The ALG-treated subgroup showed the greatest differences between treatments. Compared with patients receiving ALG alone, patients treated with ALG plus HGFs had significantly better one-year survival (100% vs. 54.5%, P < 0.05), complete remission rates (91% vs. 36%, P < 0.05), more rapid and complete hematologic recovery, greater reductions in transfusion requirements, and lower infection rates. The data suggest a potential role for rhEPO + rhGM-CSF therapy in SAA patients receiving IST.

Adolescent↗
PubMed1988

Effect of cyclosporin A on hepatocyte proliferation after partial hepatectomy in rats: comparison with standard immunosuppressive agents.

The effects of cyclosporin A on the regenerating liver were studied in rats after partial hepatectomy and were compared with those of conventional immunosuppressants such as methylprednisolone and azathioprine. In Group I, a standard hepatectomy removing two thirds of the organ was performed. In Group II, an oral dose of 10 mg/kg of cyclosporin A was given 1 day before and immediately, 24 hours, and 48 hours after the same hepatectomy. In Groups III and IV, azathioprine and methylprednisolone were administered in 8 mg/kg doses by way of the tail vein by the same protocol as in Group II. The mortality rate, liver weight restoration, and histologic and mitotic characteristics of the liver remnants, as well as serum levels of animotransferase, total bilirubin, and creatinine were examined from 24 hours to 10 days after the operation. Azathioprine and methylprednisolone substantially suppressed hepatocyte mitosis when compared with the control group; however, cyclosporin A treatment did not inhibit, but may, in fact, have stimulated liver cell proliferation. Changes in other parameters coincided with this phenomenon. The noninhibitory effect of cyclosporin A on liver regeneration has also been discussed.

Animals↗
PubMed2000

Recovery of hematopoietic progenitor cells in patients with severe aplastic anemia who obtained good clinical response with a combination therapy of immunosuppressive agents and recombinant human granulocyte colony-stimulating factor.

Seventeen patients with newly diagnosed acquired severe aplastic anemia were treated with a combination of immunosuppressive drugs consisting of anti-lymphocyte or anti-thymocyte globulin, cyclosporin A (CyA), methylprednisolone, and recombinant human granulocyte colony-stimulating factor (G-CSF). Fourteen (82%) of the 17 patients achieved good response (GR), and 3 (18%) had no response. Among the 14 GR patients, 5 (36%) later evolved clonal diseases, 1 developed myelodysplastic syndrome, and 4 developed paroxysmal nocturnal hemoglobinuria. The numbers of granulocyte-macrophage colony-forming units (CFU-GM) and erythrocyte burst-forming units were markedly low or absent in all cases before therapy. After therapy, those numbers in 13 patients among 14 responders recovered to the level of the normal control at the time of GR. However, the CFU-GM number substantially declined after that but gradually recovered again to reach a normal level over longer clinical courses. The positive rate for HLA-DRB1*1501 was 60% (3/5) among 5 CyA-dependent patients, which tended to be higher than the 20% (1/5) among 5 CyA-independent patients. Thus, immunosuppressive therapy combined with G-CSF provides a high rate of good hematological response accompanied by the apparent recovery of the hematopoietic progenitor compartments.

Adolescent↗