The anti-inflammatory potency of biologics targeting tumour necrosis factor-alpha, interleukin (IL)-17A, IL-12/23 and CD20 in hidradenitis suppurativa: an ex vivo study
Background 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.
|Persistent URL||dx.doi.org/10.1111/bjd.17641, hdl.handle.net/1765/118881|
|Journal||British Journal of Dermatology|
Vossen, A.C.Th.M, Ardon, C, van der Zee, H.H, Lubberts, E.W, & Prens, E.P. (2019). The anti-inflammatory potency of biologics targeting tumour necrosis factor-alpha, interleukin (IL)-17A, IL-12/23 and CD20 in hidradenitis suppurativa: an ex vivo study. British Journal of Dermatology, 181(2), 314–323. doi:10.1111/bjd.17641