ArticlePloS one2017
The Effect of Tacrolimus and Mycophenolic Acid on CD14+ Monocyte Activation and Function.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Electrochemotherapy of Melanoma Cutaneous Metastases in Organ Transplant Recipients: A Systematic Review of Preclinical and Clinical Studies.International journal of molecular sciences · 2023Pooled it
- Differential T Cell Signaling Pathway Activation by Tacrolimus and Belatacept after Kidney Transplantation: Post Hoc Analysis of a Randomised-Controlled Trial.Scientific reports · 2017Trial
- Modulation of the regenerative microenvironment within acellular nerve allografts using tacrolimus improves nerve regeneration.Neural regeneration research · 2026Article
- Injectable Thermoresponsive Dual Nanocarrier Hydrogel for Local Tacrolimus Delivery with a Two-Phase Release Profile.Pharmaceutics · 2026Article
- Amino acid metabolism modulates macrophage polarization: implications for autoimmune-related diseases.Frontiers in immunology · 2026Review
- Immunosuppressant imprecision: multidirectional effects on metabolism and microbiome.Clinical microbiology reviews · 2025Review
- Unraveling the Roles of Macrophages in Vascularized Composite Allotransplantation.Biomedicines · 2025Review
- FK506 Enhancement of Neuromuscular Junction Recovery After Nerve Injury Is Macrophage-Dependent.Muscle & nerve · 2025Article
- The role of monocytes and macrophages in idiopathic inflammatory myopathies: insights into pathogenesis and potential targets.Frontiers in immunology · 2025Review
- Immunosuppressant therapy averts rejection of allogeneic FKBP1A-disrupted CAR-T cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Regulation of macrophage polarization by targeted metabolic reprogramming for the treatment of lupus nephritis.Molecular medicine (Cambridge, Mass.) · 2024Review
- Endobiogenic Biology of Function Indices in a Cohort of Kidney Transplant Recipients.Medicina (Kaunas, Lithuania) · 2024Article
- Mechanism of tacrolimus in the treatment of lupus nephritis.Frontiers in pharmacology · 2024Review
- A Reversibly Thermoresponsive, Theranostic Nanoemulgel for Tacrolimus Delivery to Activated Macrophages: Formulation and In Vitro Validation.Pharmaceutics · 2023Article
- Multiple Shades of Gray-Macrophages in Acute Allograft Rejection.International journal of molecular sciences · 2023Review
- SARS-CoV-2 infection in dialysis and kidney transplant patients: immunological and serological response.Journal of nephrology · 2022Article
- A Tissue-Tended Mycophenolate-Modified Nanoparticle Alleviates Systemic Lupus Erythematosus in MRL/International journal of nanomedicine · 2022Article
- Urine Soluble CD163 Is a Promising Biomarker for the Diagnosis and Evaluation of Lupus Nephritis.Frontiers in immunology · 2022Article
- Increased macrophage activation marker soluble CD163 is associated with graft dysfunction and metabolic derangements in renal transplant recipients.Biomedical journal · 2021Article
- Immunosuppressive Agents and Infectious Risk in Transplantation: Managing the "Net State of Immunosuppression".Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Monocytes and macrophages play key roles in many disease states, including cellular and humoral rejection after solid organ transplantation (SOT). To suppress alloimmunity after SOT, immunosuppressive drug therapy is necessary. However, little is known about the effects of the immunosuppressive drugs tacrolimus and mycophenolic acid (MPA) on monocyte activation and function. Here, the effect of these immunosuppressants on monocytes was investigated by measuring phosphorylation of three intracellular signaling proteins which all have a major role in monocyte function: p38MAPK, ERK and Akt. In addition, biological functions downstream of these signaling pathways were studied, including cytokine production, phagocytosis and differentiation into macrophages. To this end, blood samples from healthy volunteers were spiked with diverse concentrations of tacrolimus and MPA. Tacrolimus (200 ng/ml) inhibited phosphorylation of p38MAPK by 30% (mean) in CD14+ monocytes which was significantly less than in activated CD3+ T cells (max 60%; p < 0.05). This immunosuppressive agent also partly inhibited p-AKT (14%). MPA, at a therapeutic concentration showed the strongest effect on p-AKT (27% inhibition). p-ERK was inhibited with a maximum of 15% after spiking with either tacrolimus or MPA. The production of IL-1β and phagocytosis by monocytes were not affected by tacrolimus concentrations, whereas MPA did inhibit IL-1β production by 50%. Monocyte/macrophage polarization was shifted to an M2-like phenotype in the presence of tacrolimus, while MPA increased the expression of M2 surface markers, including CD163 and CD200R, on M1 macrophages. These results show that tacrolimus and MPA do not strongly affect monocyte function, apart from a change in macrophage polarization, to a clinically relevant degree.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.