Compartmentalized Cytokine Responses in Hidradenitis Suppurativa

PLoS One. 2015 Jun 19;10(6):e0130522. doi: 10.1371/journal.pone.0130522. eCollection 2015.

Abstract

Background: Favorable treatment outcomes with TNF blockade led us to explore cytokine responses in hidradenitis suppurativa (HS).

Methods: Blood 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.

Results: CD14brightCD16dim 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.

Conclusions: Findings indicate compartmentalized cytokine expression in HS; high in pus but suppressed in PBMCs. This is modulated through blockade of TNF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Cytokines / metabolism*
  • Etanercept / therapeutic use
  • Female
  • Follow-Up Studies
  • Hidradenitis Suppurativa / drug therapy
  • Hidradenitis Suppurativa / metabolism
  • Hidradenitis Suppurativa / pathology*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Interleukin-17 / metabolism
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / metabolism
  • Lipopolysaccharide Receptors / metabolism
  • Male
  • Middle Aged
  • Monocytes / cytology
  • Monocytes / metabolism
  • Receptors, IgG / metabolism
  • Severity of Illness Index
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cytokines
  • IL17A protein, human
  • Immunosuppressive Agents
  • Interleukin-17
  • Interleukin-1beta
  • Lipopolysaccharide Receptors
  • Receptors, IgG
  • Tumor Necrosis Factor-alpha
  • Etanercept

Grants and funding

The study was funded by the Hellenic Institute for the Study of Sepsis. MGN was funded by a Vici grant of the Netherlands Organization for Scientific Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.