Cyclosporin, Tacrolimus, Mycophenolic Acid, and Dexamethasone Suppress Peripheral Blood Mononuclear Cell Proliferation and Inhibit Interferon-Gamma, IL-10 and IL-13 Production <em>In Vitro</em>
Objective: The primary goals of immunosuppressive therapy are to prevent graft rejection and to improve graft and patient survival. Long-term maintenance therapy after kidney transplantation includes cyclosporine A (CsA), tacrolimus (FK506), mycophenolic acid (MPA), and dexamethasone (Dex). This stu...
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| Language: | English |
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Galenos Publishing House
2024-12-01
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| Series: | Turkish Journal of Immunology |
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| Online Access: | https://jag.journalagent.com/z4/download_fulltext.asp?pdir=tji&un=TJI-84803 |
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| author | Abdel-Rahman Youssef |
| author_facet | Abdel-Rahman Youssef |
| author_sort | Abdel-Rahman Youssef |
| collection | DOAJ |
| description | Objective: The primary goals of immunosuppressive therapy are to prevent graft rejection and to improve graft and patient survival. Long-term maintenance therapy after kidney transplantation includes cyclosporine A (CsA), tacrolimus (FK506), mycophenolic acid (MPA), and dexamethasone (Dex). This study aimed to determine the effects of these immunosuppressants on the proliferation of human peripheral blood mononuclear cells (PBMC) and the production of interferon-gamma (IFN-γ), interleukin (IL)-10, and IL-13 in vitro.
Materials and Methods: Human PBMC were isolated and stimulated with an immobilized anti-CD3 (OKT3) monoclonal antibody in the absence (control) or presence of immunosuppressants. Additionally, unstimulated cells were cultured without anti-CD3 or immunosuppressants. On day 3 of cell culture, PBMC proliferation was assessed by 3H-thymidine incorporation, and cytokine production of IFN-γ, IL-10, and IL-13 was measured by ELISA.
Results: CsA, FK506, MPA, and Dex inhibited PBMC proliferation and the production of IFN-γ, IL-10, and IL-13. CsA (100-1000 ng/ mL) and FK506 (1-10 ng/mL) inhibited PBMC proliferation significantly (p<0.05). All concentrations of MPA (0.01-10 μg/mL) and Dex (10-4-10-8 M) inhibited PBMC proliferation (p<0.05). High doses of CsA (100 ng/mL), MPA (1000 ng/mL), FK506 (10 ng/mL), and Dex (10-7 M) significantly inhibited IFN-γ, IL-10, and IL-13 significantly inhibited (p<0.05), while low-dose MPA (10 ng/mL) significantly increased IL-10 and IL-13 levels (p<0.05).
Conclusion: The maintenance immunosuppressive regimen at therapeutically relevant concentrations including CsA (100 ng/mL), FK506 (10 ng/ mL), MPA (1 μg/mL), and Dex (10-6-10-7 M) suppressed PBMC proliferation and inhibited IFN-γ, IL-10, and IL-13 production in vitro. |
| format | Article |
| id | doaj-art-a913343df3474178929f9dc707835929 |
| institution | Kabale University |
| issn | 1301-109X 2147-8325 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Galenos Publishing House |
| record_format | Article |
| series | Turkish Journal of Immunology |
| spelling | doaj-art-a913343df3474178929f9dc7078359292025-01-17T08:29:34ZengGalenos Publishing HouseTurkish Journal of Immunology1301-109X2147-83252024-12-011239810510.4274/tji.galenos.2024.84803TJI-84803Cyclosporin, Tacrolimus, Mycophenolic Acid, and Dexamethasone Suppress Peripheral Blood Mononuclear Cell Proliferation and Inhibit Interferon-Gamma, IL-10 and IL-13 Production <em>In Vitro</em>Abdel-Rahman Youssef0Umm Al-Qura University College of Dental Medicine, Department of Basic and Clinical Oral Sciences, Division of Basic Medical Sciences, Makkah, Saudi ArabiaObjective: The primary goals of immunosuppressive therapy are to prevent graft rejection and to improve graft and patient survival. Long-term maintenance therapy after kidney transplantation includes cyclosporine A (CsA), tacrolimus (FK506), mycophenolic acid (MPA), and dexamethasone (Dex). This study aimed to determine the effects of these immunosuppressants on the proliferation of human peripheral blood mononuclear cells (PBMC) and the production of interferon-gamma (IFN-γ), interleukin (IL)-10, and IL-13 in vitro. Materials and Methods: Human PBMC were isolated and stimulated with an immobilized anti-CD3 (OKT3) monoclonal antibody in the absence (control) or presence of immunosuppressants. Additionally, unstimulated cells were cultured without anti-CD3 or immunosuppressants. On day 3 of cell culture, PBMC proliferation was assessed by 3H-thymidine incorporation, and cytokine production of IFN-γ, IL-10, and IL-13 was measured by ELISA. Results: CsA, FK506, MPA, and Dex inhibited PBMC proliferation and the production of IFN-γ, IL-10, and IL-13. CsA (100-1000 ng/ mL) and FK506 (1-10 ng/mL) inhibited PBMC proliferation significantly (p<0.05). All concentrations of MPA (0.01-10 μg/mL) and Dex (10-4-10-8 M) inhibited PBMC proliferation (p<0.05). High doses of CsA (100 ng/mL), MPA (1000 ng/mL), FK506 (10 ng/mL), and Dex (10-7 M) significantly inhibited IFN-γ, IL-10, and IL-13 significantly inhibited (p<0.05), while low-dose MPA (10 ng/mL) significantly increased IL-10 and IL-13 levels (p<0.05). Conclusion: The maintenance immunosuppressive regimen at therapeutically relevant concentrations including CsA (100 ng/mL), FK506 (10 ng/ mL), MPA (1 μg/mL), and Dex (10-6-10-7 M) suppressed PBMC proliferation and inhibited IFN-γ, IL-10, and IL-13 production in vitro.https://jag.journalagent.com/z4/download_fulltext.asp?pdir=tji&un=TJI-84803cyclosporintacrolimusmycophenolic aciddexamethasonepbmc proliferationifn-γil-10il-13 |
| spellingShingle | Abdel-Rahman Youssef Cyclosporin, Tacrolimus, Mycophenolic Acid, and Dexamethasone Suppress Peripheral Blood Mononuclear Cell Proliferation and Inhibit Interferon-Gamma, IL-10 and IL-13 Production <em>In Vitro</em> Turkish Journal of Immunology cyclosporin tacrolimus mycophenolic acid dexamethasone pbmc proliferation ifn-γ il-10 il-13 |
| title | Cyclosporin, Tacrolimus, Mycophenolic Acid, and Dexamethasone Suppress Peripheral Blood Mononuclear Cell Proliferation and Inhibit Interferon-Gamma, IL-10 and IL-13 Production <em>In Vitro</em> |
| title_full | Cyclosporin, Tacrolimus, Mycophenolic Acid, and Dexamethasone Suppress Peripheral Blood Mononuclear Cell Proliferation and Inhibit Interferon-Gamma, IL-10 and IL-13 Production <em>In Vitro</em> |
| title_fullStr | Cyclosporin, Tacrolimus, Mycophenolic Acid, and Dexamethasone Suppress Peripheral Blood Mononuclear Cell Proliferation and Inhibit Interferon-Gamma, IL-10 and IL-13 Production <em>In Vitro</em> |
| title_full_unstemmed | Cyclosporin, Tacrolimus, Mycophenolic Acid, and Dexamethasone Suppress Peripheral Blood Mononuclear Cell Proliferation and Inhibit Interferon-Gamma, IL-10 and IL-13 Production <em>In Vitro</em> |
| title_short | Cyclosporin, Tacrolimus, Mycophenolic Acid, and Dexamethasone Suppress Peripheral Blood Mononuclear Cell Proliferation and Inhibit Interferon-Gamma, IL-10 and IL-13 Production <em>In Vitro</em> |
| title_sort | cyclosporin tacrolimus mycophenolic acid and dexamethasone suppress peripheral blood mononuclear cell proliferation and inhibit interferon gamma il 10 and il 13 production em in vitro em |
| topic | cyclosporin tacrolimus mycophenolic acid dexamethasone pbmc proliferation ifn-γ il-10 il-13 |
| url | https://jag.journalagent.com/z4/download_fulltext.asp?pdir=tji&un=TJI-84803 |
| work_keys_str_mv | AT abdelrahmanyoussef cyclosporintacrolimusmycophenolicacidanddexamethasonesuppressperipheralbloodmononuclearcellproliferationandinhibitinterferongammail10andil13productioneminvitroem |