Trial reportPloS one2013
Profiling sirolimus-induced inflammatory syndrome: a prospective tricentric observational study.
Trial report in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort: Immunological, physical performance, and cognitive effects.Experimental gerontology · 2018Trial
- Beyond the Prevention of Anti-drug Antibody Formation with Uricase Therapy: Mechanistic Roles of DMARDs in Modifying Gout Flare Risk.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Dual inhibition of mTOR and calcineurin pathways mitigates missing self-induced NK cell-mediated microvascular rejection.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Rapamycin ExacerbatesJournal of inflammation research · 2023Article
- Absence of Mortality Differences Between the First and Second COVID-19 Waves in Kidney Transplant Recipients.Kidney international reports · 2022Article
- Clinically available immunosuppression averts rejection but not systemic inflammation after porcine islet xenotransplant in cynomolgus macaques.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2022Article
- mTOR direct crosstalk with STAT5 promotes de novo lipid synthesis and induces hepatocellular carcinoma.Cell death & disease · 2019Article
- Emerging Perspectives on mTOR Inhibitor-Associated Pneumonitis in Breast Cancer.The oncologist · 2018Review
- Mammalian Target of Rapamycin: A Target for (Lung) Diseases and Aging.Annals of the American Thoracic Society · 2016Review
- Liver damage, inflammation, and enhanced tumorigenesis after persistent mTORC1 inhibition.Cell metabolism · 2014Article
- Immune responses of macrophages and dendritic cells regulated by mTOR signalling.Biochemical Society transactions · 2013Review
- Systemic and nonrenal adverse effects occurring in renal transplant patients treated with mTOR inhibitors.Clinical & developmental immunology · 2013Review
- Sirolimus is effective in autoimmune lymphoproliferative syndrome-type III: A pedigree case report with homozygous variation PRKCD.International journal of immunopathology and pharmacologyArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe use of the immunosuppressant sirolimus in kidney transplantation has been made problematic by the frequent occurrence of various side effects, including paradoxical inflammatory manifestations, the pathophysiology of which has remained elusive.
methods30 kidney transplant recipients that required a switch from calcineurin inhibitor to sirolimus-based immunosuppression, were prospectively followed for 3 months. Inflammatory symptoms were quantified by the patients using visual analogue scales and serum samples were collected before, 15, 30, and 90 days after the switch.
results66% of patients reported at least 1 inflammatory symptom, cutaneo-mucosal manifestations being the most frequent. Inflammatory symptoms were characterized by their lability and stochastic nature, each patient exhibiting a unique clinical presentation. The biochemical profile was more uniform with a drop of hemoglobin and a concomitant rise of inflammatory acute phase proteins, which peaked in the serum 1 month after the switch. Analyzing the impact of sirolimus introduction on cytokine microenvironment, we observed an increase of IL6 and TNFα without compensation of the negative feedback loops dependent on IL10 and soluble TNF receptors. IL6 and TNFα changes correlated with the intensity of biochemical and clinical inflammatory manifestations in a linear regression model.
conclusionsSirolimus triggers a destabilization of the inflammatory cytokine balance in transplanted patients that promotes a paradoxical inflammatory response with mild stochastic clinical symptoms in the weeks following drug introduction. This pathophysiologic mechanism unifies the various individual inflammatory side effects recurrently reported with sirolimus suggesting that they should be considered as a single syndromic entity.
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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.