Altered expression of IL-10 family cytokines in monocytes from CRMO patients result in enhanced IL-1β expression and release

Clin Immunol. 2015 Dec;161(2):300-7. doi: 10.1016/j.clim.2015.09.013. Epub 2015 Sep 25.


Chronic recurrent multifocal osteomyelitis (CRMO) is characterized by reduced activation of protein kinases ERK1 and 2 in monocytes resulting in impaired IL-10 expression. IL10 and its homologs IL19 and IL20 are organized in the IL10 cluster on chromosome 1q32. IL-10 and IL-19 are immune-regulatory cytokines, while IL-20 acts in a pro-inflammatory manner. The NLRP3 inflammasome, a multi-protein complex forming in response to innate stimuli, mediates IL-1β cleavage and release. Here, we investigated IL-10-related cytokine expression in CRMO monocytes, underlying molecular events, and effects on inflammatory responses. We observed reduced anti-inflammatory IL-10 and IL-19 expression, and enhanced IL-20 expression in CRMO monocytes. Reduced IL-10 and IL-19 expression was associated with impaired Sp-1 recruitment to regulatory regions, contributing to NLRP3 inflammasome activation, which may induce inflammatory bone-loss. Our findings underscore the importance of balanced receptor-, cell-, and tissue-specific cytokine expression for immune homeostasis, providing additional arguments for cytokine blocking strategies in CRMO.

Keywords: Bone; CNO; CRMO; Cytokine; IL-10; Inflammasome; Inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / metabolism
  • Cell Line, Tumor
  • Cells, Cultured
  • Child
  • DNA Methylation
  • Enzyme-Linked Immunosorbent Assay
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Flow Cytometry
  • Gene Expression*
  • Humans
  • Inflammasomes / metabolism
  • Interleukin-10 / genetics*
  • Interleukin-10 / metabolism
  • Interleukin-1beta / genetics*
  • Interleukin-1beta / metabolism
  • Interleukins / genetics*
  • Interleukins / metabolism
  • Monocytes / metabolism*
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Osteomyelitis / genetics
  • Osteomyelitis / metabolism
  • Osteomyelitis / pathology
  • Promoter Regions, Genetic / genetics
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sp1 Transcription Factor / genetics
  • Sp1 Transcription Factor / metabolism


  • Carrier Proteins
  • IL19 protein, human
  • Inflammasomes
  • Interleukin-1beta
  • Interleukins
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Sp1 Transcription Factor
  • Interleukin-10
  • Extracellular Signal-Regulated MAP Kinases
  • interleukin 20

Supplementary concepts

  • Chronic recurrent multifocal osteomyelitis