The anti‐inflammatory potency of biologics targeting tumour necrosis factor‐α, interleukin ( IL )‐17A, IL ‐12/23 and CD 20 in hidradenitis suppurativa: an ex vivo study
2019
textabstractBackground Biologics targeting inflammatory mediators can achieve clinical
improvements in hidradenitis suppurativa (HS). However, their clinical efficacy
shows great interpatient variability in daily practice.
Objectives To investigate the anti-inflammatory potency of a selection of currently
available biologics and prednisolone for the treatment of HS in an ex vivo skin culture system using lesional HS biopsies.
Methods Lesional skin samples from 10 patients with HS and skin samples from
five healthy controls were cultured ex vivo and exposed to prednisolone or biologics targeting tumour necrosis factor (TNF)-a, interleukin (IL)-17A, IL-12/23p40
or CD20 (adalimumab, infliximab, secukinumab, ustekinumab and rituximab,
respectively). Real-time quantitative polymerase chain reaction 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 < 0001). The protein
production of the proinflammatory cytokines TNF-a, interferon c, IL-1b, IL-6 and
IL-17A was significantly inhibited by adalimumab, infliximab, ustekinumab, prednisolone (all P < 0001) and rituximab (P = 00071), but not by secukinumab
(P = 00663). On both mRNA and protein levels, 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 mRNA expression levels of inflammatory markers in healthy control skin was
observed only for TNF-a inhibitors (P < 0001) and prednisolone (P = 00015).
Conclusions This ex vivo study suggests that TNF-a inhibitors and prednisolone are
the most powerful inhibitors of proinflammatory cytokines and AMPs in HS
lesional skin, which concurs with our clinical experience in patients with HS.
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