PMID- 20450974 OWN - NLM STAT- MEDLINE DCOM- 20101223 LR - 20211203 IS - 1878-5492 (Electronic) IS - 0966-3274 (Linking) VI - 23 IP - 3 DP - 2010 Jul TI - Mycophenolic acid and intravenous immunoglobulin exert an additive effect on cell proliferation and apoptosis in the mixed lymphocyte reaction. PG - 117-20 LID - 10.1016/j.trim.2010.04.009 [doi] AB - BACKGROUND: Intravenous immunoglobulin (IVIG) has known immunomodulatory effects in autoimmune diseases and transplantation and is commonly used in desensitization protocols and for treatment of antibody-mediated rejection (AMR). IVIG inhibits the MLR and induces apoptosis in immune cells. Mycophenolate mofetil inhibits immune cell proliferation and is an effective immunsuppressive agent. Here, we examined the possible synergistic effects of combined MMF and IVIG on cell proliferation and apoptosis induction in the MLR. METHODS: Two-way MLRs were performed with mycophenolic acid (MPA), IVIG and both in combination. Cell proliferation and apoptosis were detected by 3H-thymidine incorporation and Annexin flow cytometry, respectively. RESULTS: IVIG (1-10mg/ml) or MPA (0.01-0.25 microg/ml) alone inhibited cell proliferation in the MLR in a dose-dependent manner. MPA at 0.01-0.03 microg/ml showed minimal inhibition, but the addition of 5 and 10mg/ml IVIG increased inhibition significantly (p<0.05) to 43% and 64%, respectively. Annexin V positive cell number was significantly higher in IVIG (5mg/ml) treated CD19+ cells (68+/-13% vs. 43+/-12%, p=0.001) compared to untreated cells and to a lesser degree in CD3+ cells (29+/-7% vs. 25+/-10 %, p=0.02). MPA (0.25-10 microg/ml) alone neither induced nor inhibited apoptosis. Addition of MPA had no effect on apoptosis induced by IVIG. CONCLUSION: 1) Combining low concentrations of IVIG (5-10 mg/ml) and MPA (0.01-0.03 microg/ml)has an additive effect on inhibition of cell proliferation in the MLR. 2) MPA alone neither induces nor inhibits apoptosis in T or B cells in the MLR, and has no effect on apoptosis induced by IVIG. These in vitro observations may have implications for modification of therapeutic approaches to protocols utilizing IVIG for desensitization and immune modulation. CI - 2010 Elsevier B.V. All rights reserved. FAU - Sharma, Kavita G AU - Sharma KG AD - Transplant Immunology Laboratory, Comprehensive Transplant Center, Cedars-Sinai Medical Center/UCLA School of Medicine, 8700 Beverly Blvd., Los Angeles, CA 90048, USA. FAU - Radha, Raju AU - Radha R FAU - Pao, Andy AU - Pao A FAU - Amet, Nurmamet AU - Amet N FAU - Baden, Lara AU - Baden L FAU - Jordan, Stanley C AU - Jordan SC FAU - Toyoda, Mieko AU - Toyoda M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100505 PL - Netherlands TA - Transpl Immunol JT - Transplant immunology JID - 9309923 RN - 0 (Antigens, CD19) RN - 0 (CD3 Complex) RN - 0 (Immunoglobulins, Intravenous) RN - 0 (Immunosuppressive Agents) RN - HU9DX48N0T (Mycophenolic Acid) SB - IM MH - Antigens, CD19/biosynthesis MH - Apoptosis/drug effects/immunology MH - B-Lymphocytes/*drug effects/immunology/metabolism/pathology MH - CD3 Complex/biosynthesis MH - Cell Proliferation/drug effects MH - Cell Separation MH - Cells, Cultured MH - Drug Synergism MH - Flow Cytometry MH - Humans MH - Immunoglobulins, Intravenous/*pharmacology MH - Immunosuppression Therapy MH - Immunosuppressive Agents/*pharmacology MH - Lymphocyte Culture Test, Mixed MH - Mycophenolic Acid/*pharmacology MH - T-Lymphocytes/*drug effects/immunology/metabolism/pathology MH - Transplantation Immunology EDAT- 2010/05/11 06:00 MHDA- 2010/12/25 06:00 CRDT- 2010/05/11 06:00 PHST- 2010/02/05 00:00 [received] PHST- 2010/04/20 00:00 [revised] PHST- 2010/04/26 00:00 [accepted] PHST- 2010/05/11 06:00 [entrez] PHST- 2010/05/11 06:00 [pubmed] PHST- 2010/12/25 06:00 [medline] AID - S0966-3274(10)00031-6 [pii] AID - 10.1016/j.trim.2010.04.009 [doi] PST - ppublish SO - Transpl Immunol. 2010 Jul;23(3):117-20. doi: 10.1016/j.trim.2010.04.009. Epub 2010 May 5.