The IL-1 Pathway Is Hyperactive in Hidradenitis Suppurativa and Contributes to Skin Infiltration and Destruction

J Invest Dermatol. 2019 Jun;139(6):1294-1305. doi: 10.1016/j.jid.2018.11.018. Epub 2018 Dec 5.


Hidradenitis suppurativa (HS) (also designated acne inversa) is a chronic inflammatory disease characterized by painful purulent skin lesions and progressive destruction of skin architecture. Despite the high burden for the patients, pathogenetic pathways underlying HS alterations remain obscure. When we examined the HS cytokine pattern, IL-1β turned out to be a highly prominent cytokine, overexpressed even compared with psoriatic lesions. Analyses of IL-1β-induced transcriptome in various cell types showed overlapping profiles, with upregulations of molecules causing immune cell infiltration and extracellular matrix degradation, and of specific cytokines including IL-6, IL-32, and IL-36. Matching cellular IL-1 receptor levels, dermal fibroblasts showed both the strongest and broadest IL-1β response, which was not clearly shared or strengthened by other cytokines. The IL-1β signature was specifically present in HS lesions and could be reversed by application of IL-1 receptor antagonist. Search for blood parameters associated with IL-1β pathway activity in HS identified serum amyloid A, which was synergistically induced by IL-1β and IL-6 in hepatocytes. Consequently, strongly elevated blood serum amyloid A levels in HS correlated positively with the extent of inflammatory skin alterations. In summary, the IL-1β pathway represents a pathogenetic cascade, whose activity may be therapeutically targeted and monitored by blood SAA levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biopsy
  • Case-Control Studies
  • Cells, Cultured
  • Extracellular Matrix / immunology
  • Extracellular Matrix / metabolism
  • Female
  • Fibroblasts / immunology
  • Fibroblasts / metabolism
  • Hepatocytes / immunology
  • Hepatocytes / metabolism
  • Hidradenitis Suppurativa / blood
  • Hidradenitis Suppurativa / immunology*
  • Hidradenitis Suppurativa / pathology
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / metabolism
  • Interleukin-1beta / immunology
  • Interleukin-1beta / metabolism*
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism*
  • Keratinocytes / immunology
  • Keratinocytes / metabolism
  • Male
  • Middle Aged
  • Primary Cell Culture
  • Receptors, Interleukin-1 / antagonists & inhibitors
  • Receptors, Interleukin-1 / metabolism*
  • Serum Amyloid A Protein / analysis
  • Serum Amyloid A Protein / immunology
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Skin / cytology
  • Skin / immunology
  • Skin / pathology
  • Up-Regulation
  • Young Adult


  • IL1B protein, human
  • IL6 protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1beta
  • Interleukin-6
  • Receptors, Interleukin-1
  • Serum Amyloid A Protein