Evidence map›Paper›PMID 27669117›Full record

ArticleClinical and experimental immunology2017

Anti-inflammatory effects of infliximab in mice are independent of tumour necrosis factor α neutralization.

M B Assas, S E Levison, M Little, H England, L Battrick, J Bagnall, J T McLaughlin, P Paszek, K J Else, J L Pennock

Open access · hybridAbstract read
In one paragraph

Article in Clinical and experimental immunology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 17% 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

23 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.

  1. Pooled it
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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

10 authors at 3 institutions in 2 countries.

M B AssasFaculty of Applied Medical Sciences, King AbdulAziz University, Jeddah, Saudi Arabia.
S E LevisonManchester Royal Infirmary, Manchester, UK.
M LittleSchool of Biological Sciences, Faculty of Medicine Biology and Health, University of Manchester, Manchester, UK.
H EnglandSchool of Biological Sciences, Faculty of Medicine Biology and Health, University of Manchester, Manchester, UK.
L BattrickSchool of Biological Sciences, Faculty of Medicine Biology and Health, University of Manchester, Manchester, UK.
J BagnallSchool of Biological Sciences, Faculty of Medicine Biology and Health, University of Manchester, Manchester, UK.
J T McLaughlinSchool of Biological Sciences, Faculty of Medicine Biology and Health, University of Manchester, Manchester, UK.
P PaszekSchool of Biological Sciences, Faculty of Medicine Biology and Health, University of Manchester, Manchester, UK.
K J ElseSchool of Biological Sciences, Faculty of Medicine Biology and Health, University of Manchester, Manchester, UK.
J L PennockSchool of Biological Sciences, Faculty of Medicine Biology and Health, University of Manchester, Manchester, UK.
University of Manchester · GBKing Abdulaziz University · SAManchester Royal Infirmary · GB

Funding

Biotechnology and Biological Sciences Research Council BB/I017976/1Biotechnology and Biological Sciences Research Council BB/K003097/1Medical Research Council G0800456
6 · The paper itself

Abstract

Infliximab (IFX) has been used repeatedly in mouse preclinical models with associated claims that anti-inflammatory effects are due to inhibition of mouse tumour necrosis factor (TNF)-α. However, the mechanism of action in mice remains unclear. In this study, the binding specificity of IFX for mouse TNF-α was investigated ex vivo using enzyme-linked immunosorbent assay (ELISA), flow cytometry and Western blot. Infliximab (IFX) did not bind directly to soluble or membrane-bound mouse TNF-α nor did it have any effect on TNF-α-induced nuclear factor kappa B (NF-κB) stimulation in mouse fibroblasts. The efficacy of IFX treatment was then investigated in vivo using a TNF-α-independent Trichuris muris-induced infection model of chronic colitis. Infection provoked severe transmural colonic inflammation by day 35 post-infection. Colonic pathology, macrophage phenotype and cell death were determined. As predicted from the in-vitro data, in-vivo treatment of T. muris-infected mice with IFX had no effect on clinical outcome, nor did it affect macrophage cell phenotype or number. IFX enhanced apoptosis of colonic immune cells significantly, likely to be driven by a direct effect of the humanized antibody itself. We have demonstrated that although IFX does not bind directly to TNF-α, observed anti-inflammatory effects in other mouse models may be through host cell apoptosis. We suggest that more careful consideration of xenogeneic responses should be made when utilizing IFX in preclinical models.

Indexed as

AnimalsAntibodies, BlockingApoptosisCells, CulturedColitisEpitopesFibroblastsHumansInfliximabMacrophagesMaleMiceMice, Inbred AKRMice, KnockoutProtein BindingTrichuriasisAntibodies, BlockingEpitopesInfliximabTumor Necrosis Factor-alphaantibodyinflammationmacrophagemucosa

Identifiers

PMID27669117
PMCPMC5217947
OpenAlexW2565319519

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.