Compartmentalized Cytokine Responses in Hidradenitis Suppurativa

Abstract

BackgroundFavorable treatment outcomes with TNF blockade led us to explore cytokine responses in hidradenitis suppurativa (HS).MethodsBlood monocytes of 120 patients and 24 healthy volunteers were subtyped by flow cytometry. Isolated blood mononuclear cells (PBMCs) were stimulated for cytokine production; this was repeated in 13 severe patients during treatment with etanercept. Cytokines in pus were measured.ResultsCD14brightCD16dim inflammatory monocytes and patrolling monocytes were increased in Hurley III patients. Cytokine production by stimulated PBMCs was low compared to controls but the cytokine gene copies did not differ, indicating post-translational inhibition. The low production of IL-17 was restored, when cells were incubated with adalimumab. In pus, high concentrations of pro-inflammatory cytokines were detected. Based on the patterns, six different cytokine profiles were discerned, which are potentially relevant for the choice of treatment. Clinical improvement with etanercept was predicted by increased production of IL-1β and IL-17 by PBMCs at week 8.ConclusionsFindings indicate compartmentalized cytokine expression in HS; high in pus but suppressed in PBMCs. This is modulated through blockade of TNF.

Leukocyte Profile in Peripheral Blood and Neutrophil-Lymphocyte Ratio in Hidradenitis Suppurativa: A Comparative Cross-Sectional Study of 462 Cases

“…A previous study investigating blood monocyte subtypes in HS patients found certain monocyte subtypes increased in Hurley stage III, but low cytokine production from stimulated blood mononuclear cells [35]. Our study found HS to be associated with higher levels of monocytes compared to controls.…”

A guiding map for inflammation

“…Psoriasis involves systemic inflammatory responses and frequent comorbidities are rheumatological or cardiovascular in nature47. In hidradenitis suppurativa, also known as acne inversa, a devastating skin disorder bearing the characteristics of both auto-inflammatory and auto-immune disorders, histopathology reveals heavy lesional deposits of TNF, IL-1β, IL-23 and IL-17, as well as activation of both CD4 + and CD8 + T cells 48.…”

Interferon-gamma (IFN-γ) is Elevated in Wound Exudate from Hidradenitis Suppurativa

“…Prior studies investigating cytokine profiles in HS patients have shown high levels of proinflammatory cytokines in pus extracted from HS lesions but low cytokine production in peripheral blood mononuclear cells (PBMC) from patients compared to normal controls (Kanni, Tzanetakou et al 2015). This suggests that there is compartmentalized cytokine expression in HS.…”