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

Abstract

Hidradenitis suppurativa (HS) is a chronic recurrent inflammatory disease of apocrine glands which affects 1% to 4% of young adults. The purpose of this study was to investigate inflammatory cytokines in effluent from HS lesions and to identify potential local drivers of inflammation in HS. Wound fluid specimens from HS patients (n=8) and age-matched chronic wound patients (n=8) were selected for analysis. The Hidradenitis Suppurativa Score (HSS) was used to determine extent of HS activity. Cytokine analysis was conducted using Meso Scale Discovery cytokine and proinflammatory panels. Interferon-gamma (IFN-γ) was significantly elevated in the HS effluent compared to chronic wounds (1418 ± 1501 pg/ml compared to 102.5 ± 138 pg/ml, p 0.027). HS effluent also had significantly higher levels of TNF-β (9.24 ± 7.22 pg/ml compared to 1.65 ± 2.14 pg/ml, p 0.03). There was no significant difference in any other cytokines. There was no significant difference in demographics in the HS compared to chronic wound cohorts. Mean HSS in the HS cohort was 68.88 (SD ± 41.45). In this proof of concept pilot study, IFN- γ was significantly elevated in HS effluent. TNF-β/LT-α levels were also elevated in HS, although the levels were more modest. Further studies should focus on molecular drivers of tissue injury in HS, and the relationship between HS effluent cytokine profile and disease activity.

Transcriptome patterns in hidradenitis suppurativa: support for the role of antimicrobial peptides and interferon pathways in disease pathogenesis

“…IFN‐γ is crucial for Th1 differentiation and activation, and also activates macrophages resulting in granuloma formation . Prior studies have demonstrated significant elevation of IFN‐γ in the exudate from HS lesions . The current study further demonstrates upregulation of multiple molecules in IFN pathways in HS, providing additional data to support these pathways as critical drivers in HS pathogenesis and as potential therapeutic targets.…”

“…The molecular drivers of HS are poorly understood but inflammatory pathways and immune dysregulation likely play a role. Progression of HS severity is accompanied by increased levels of interleukin (IL)‐1, IL‐10, IL‐17, tumour necrosis factor (TNF)‐α, interferon (IFN)‐γ, S100A8, S100A9 and caspase‐1 in the tissues and lesion effluent . Suppression of IL‐22 also plays a role in pathogenesis .…”

Review of Current Immunologic Therapies for Hidradenitis Suppurativa

“…In this double-blind randomized trial, anakinra efficacy correlates with alterations in cytokine production by PBMC, with increased production of IFN- γ in the placebo arm and increased IL-22 in the anakinra treated group. These observations correlate with studies investigating cytokine production in HS lesion tissue and effluent in which IFN- γ has been shown to be elevated in active disease [ 18 ], and IL-22 production is reduced [ 19 ], providing further evidence that targeting biologic response pathways in HS can provide novel therapeutic options for this disease.…”

“…Recent studies suggest that tumor necrosis factor α (TNF α ) is elevated in active lesions. In addition, interferon-gamma (IFN- γ ) has been shown to be elevated in lesion effluent [ 18 ], and suppression of IL22 [ 19 ] along with the IL12/23 pathways is thought to play a role in pathogenesis [ 20 , 21 ].…”

Cytokine Pathways and Investigational Target Therapies in Hidradenitis Suppurativa

“…IFN-γ is secreted by Th1 cells, induces Th1-attracting chemokines such as CXCL10, and activates dermal endothelial cells and macrophages allowing the infiltration of immune cells from the bloodstream [ 82 ]. IFN-γ mRNA and protein expression have been shown to be elevated compared to those in healthy controls in skin lesions and wound exudate, and its contribution has been assessed by several high-powered studies [ 77 , 83 , 84 ].…”