Evidence map›Paper›PMID 27275747›Full record

ArticlePloS one2016

Immunoregulatory Effects of Everolimus on In Vitro Alloimmune Responses.

Josh Levitsky, Joshua Miller, Xuemei Huang, Lorenzo Gallon, Joseph R Leventhal, James M Mathew

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.0field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 13 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Josh LevitskyDivision of Gastroenterology & Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.
Joshua MillerComprehensive Transplant Center, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.
Xuemei HuangComprehensive Transplant Center, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.
Lorenzo GallonComprehensive Transplant Center, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.
Joseph R LeventhalComprehensive Transplant Center, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.
James M MathewComprehensive Transplant Center, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.
Northwestern University · US

Funding

REGULATORY T AND B CELL CIRCUITS IN TRANSPLANTATIONR01DK025243 · NIDDK · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI MILLER, JOSHUA · 1986 to 2010
$3.9M
NIDDK NIH HHS R01 DK025243
6 · The paper itself

Abstract

Everolimus (EVL) is a novel mTOR-inhibitor similar to sirolimus (SRL) that is used in organ transplant recipients, often in combination with tacrolimus (TAC) or mycophenolate (MPA). The current study aims to determine its effects on regulatory T cells. Increasing concentrations of EVL, MPA and TAC alone or in combination were added to MLRs of healthy volunteers. Lymphoproliferation by 3H-TdR incorporation and the percentage of newly generated CD4+CD127-CD25+FOXP3+ (total Treg) and CD4+CD127-CD25HighFOXP3+ (natural Treg) in CFSE labeled responder cells were assessed by flow cytometry. In comparison to medium controls, EVL and other agents dose-dependently inhibited 3H-TdR incorporation in HLA-2DR-matched and HLA-mismatched MLRs (n = 3-10). However, EVL significantly amplified newly generated total and natural Tregs in CFSE labeled responder cells (p<0.05) at all concentrations, while MPA and SRL did this only at sub-therapeutic concentrations and inhibited at therapeutic levels. In contrast, TAC inhibited newly generated Tregs at all concentrations. When tested in combination with TAC, EVL failed to reverse TAC inhibition of Treg generation. Combinations of EVL and low concentrations of MPA inhibited proliferation and amplified Treg generation in an additive manner when compared to medium controls or each drug tested alone (p<0.05). The relative tolerogenic effect from high to low was EVL > SRL> MPA > TAC. If the results from these in vitro studies are extrapolated to clinical transplantation, it would suggest EVL plus low concentrations of MPA may be the most tolerogenic combination.

Indexed as

Antigens, CDCell ProliferationCells, CulturedDose-Response Relationship, DrugEverolimusFemaleHumansImmune ToleranceImmunosuppressive AgentsMaleMycophenolic AcidTacrolimusT-Lymphocytes, RegulatoryAntigens, CDEverolimusImmunosuppressive AgentsMycophenolic AcidTacrolimus

Identifiers

PMID27275747
PMCPMC4898829
OpenAlexW2417241414

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.