Abstract
Tocilizumab,etanerceptandabataceptarebiologicaldrugsusedinthetherapyofRheumatoidArthritis
(RA). Theirmechanismofactioniswelldocumentedbuttheirdirecteffectsonhumanmonocytes/
macrophageshavenotbeenfullyinvestigated.Theobjectiveofthisstudywastoevaluate in vitro the
influence ofthesedrugsonmonocytes/macrophagesfromhealthyvolunteers.
Human monocyteswereisolatedfromhealthyanonymousvolunteersandculturedassuchordif-
ferentiatedtomonocyte-derivedmacrophages(MDMs).Theeffectoftocilizumab,etanerceptandaba-
tacept (atconcentrationssimilartothoseinplasmaofpatients)onsuperoxideanionproduction,matrix
metalloproteinase-9(MMP-9)geneexpressionandactivity,PeroxisomeProliferator-ActivatedReceptor
(PPAR)γ expressionandcellphenotypewasevaluated.
Exposure ofmonocytes/macrophagestotocilizumab,etanerceptorabataceptresultedinasignificant
decrease ofthePMA-inducedsuperoxideanionproduction.Interestingly,theexpressionofPPARγ was
significantly increasedonlybytocilizumab,whileetanerceptwastheonlyoneabletosignificantly re-
duce MMP-9geneexpressionandinhibittheLPS-inducedMMP-9activityinmonocytes.Wheneta-
nerceptandabataceptwereaddedtothedifferentiatingmedium,bothsignificantly reducedtheamount
of CD206þMDM.
This studydemonstratesthatetanercept,abataceptandtocilizumabaffectdifferentlyhuman
monocytes/macrophages.Inparticular,theIL-6antagonisttocilizumabseemstobemoreeffectivein
inducing ananti-inflammatory phenotypeofmonocytes/macrophagescomparedtoetanerceptand
abatacept, alsoinlightoftheup-regulationofPPARγ whose anti-inflammatoryeffectsarewellre-
cognised.
| Lingua originale | Inglese |
|---|---|
| pagine (da-a) | 33-37 |
| Numero di pagine | 5 |
| Rivista | European Journal of Pharmacology |
| Volume | 780 |
| DOI | |
| Stato di pubblicazione | Pubblicato - 2016 |
Keywords
- Monocytes/macrophages Inflammation Biological drugs
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