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In vitro effects of everolimus and intravenous immunoglobulin on cell proliferation and apoptosis induction in the mixed lymphocyte reaction.
MedLine Citation:
PMID:  20609387     Owner:  NLM     Status:  In-Process    
Targeting multiple pathways in the activation of alloimmune responses by multi-drug immunosuppressive regimens with complementary mechanisms of action enhances allograft survival and improves quality of life, owing to the reduction of adverse drug effects. In this report we investigated the effect of the combination of everolimus and intraveneous immunoglobulin (IVIG) on cell proliferation and apoptosis induction in human two-way mixed lymphocyte reaction (MLR). Everolimus alone (0.1-50 ng/ml) and IVIG (1-10 mg/ml) alone inhibited cell proliferation in a dose-dependent manner (16.4-67.2% and 12.1-66.3% inhibition, respectively). The inhibition by everolimus was not enhanced in the presence of 1 mg/ml IVIG. Addition of 10 and 50 ng/ml everolimus increased the inhibitory effect of 5 and 10 mg/ml IVIG, but only by 10-27%. Addition of 0.1 and 1 ng/ml everolimus did not increase IVIG's inhibitory effects. Apoptosis was significantly higher in IVIG (5 mg/ml)-treated CD19+ cells and less so in CD3+ cells as assessed by Annexin V and TUNEL assays. However, everolimus (0.1-50 ng/ml) did not induced apoptosis or alter apoptosis induced by IVIG. These results suggest that everolimus is a potent inhibitor of immune cell proliferation but does not act additively or synergistically with IVIG when analyzed in this in vitro system.
Nurmamet Amet; Mercedes Gacad; Anna Petrosyan; Andy Pao; Stanley C Jordan; Mieko Toyoda
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-06
Journal Detail:
Title:  Transplant immunology     Volume:  23     ISSN:  1878-5492     ISO Abbreviation:  Transpl. Immunol.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9309923     Medline TA:  Transpl Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  170-3     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier B.V. All rights reserved.
Transplant Immunology Laboratory, Comprehensive Transplant Center, Cedars-Sinai Medical Center/UCLA School of Medicine, 8700 Beverly Blvd., SSB111, Los Angeles, CA 90048, USA.
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