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Παρασκευή 18 Ιανουαρίου 2019

The anti‐inflammatory potency of biologics targeting TNF‐α, IL‐17A, IL‐12/23 and CD20 in hidradenitis suppurativa: an ex vivo study

Abstract

Background

Biologics targeting inflammatory mediators are able to clinically improve hidradenitis suppurativa (HS). However, their clinical efficacy shows great inter‐patient variability in daily practice.

Objective

To investigate the anti‐inflammatory potency of a selection of currently available biologics for the treatment of HS in an ex vivo skin culture system using lesional HS biopsies.

Methods

Lesional skin samples of ten HS patients and skin samples of five healthy controls were cultured ex vivo and exposed to prednisolone or biologics targeting TNF‐α, IL‐17A, IL‐12/23p40, or CD20, respectively adalimumab, infliximab, secukinumab, ustekinumab and rituximab. Real‐Time quantitative PCR and cytokine bead arrays were used to measure the inhibitory effect of the biologics on cytokines and antimicrobial peptides (AMPs).

Results

The relative mRNA expression of all tested cytokines and AMPs was significantly downregulated by all anti‐inflammatory agents (p<0·0001). The protein production of the pro‐inflammatory cytokines TNF‐α, IFN‐ɣ, IL‐1ß, IL‐6, and IL‐17A was significantly inhibited by adalimumab, infliximab, ustekinumab, prednisolone (all p<0·0001) and rituximab (p=0·0071), but not by secukinumab (p=0·0663). On both mRNA and protein level, adalimumab, infliximab and prednisolone reduced the levels of a broader mix of individual cytokines than secukinumab, ustekinumab and rituximab. Moreover, a significant inhibitory effect on the mRNA expression levels of inflammatory markers in healthy control skin was observed only for prednisolone (p=0·0015) and the TNF‐α inhibitors (p<0·0001).

Conclusions

This ex vivo study suggests that TNF‐α inhibitors and prednisolone are the most powerful inhibitors of pro‐inflammatory cytokines and AMPs in HS lesional skin, which is in accordance with our clinical experience in patients with HS.

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