Interleukin-1 in monocyte activation phenotypes in systemic juvenile idiopathic arthritis: Observations from a clinical trial of rilonacept, an interleukin-1 inhibitor Academic Article uri icon

Overview

MeSH Major

  • Gene Rearrangement, B-Lymphocyte
  • Genes, Immunoglobulin
  • Immunoglobulin G
  • Immunoglobulin M
  • Immunoglobulin Variable Region
  • Rheumatoid Factor

abstract

  • Systemic juvenile idiopathic arthritis (sJIA) is a childhood rheumatic disease of unknown origin. Dysregulated innate immunity is implicated in disease pathology. We investigated if IL-1 inhibition affects circulating cytokines and monocyte gene expression. CD14+ monocytes from patients in the RAPPORT trial were analyzed by RT-PCR for expression of IL1B and transcription factors associated with monocyte activation. Serum IL-1ra decreased with treatment, and IL-18BP transiently increased. Serum levels of IL-1β, IL-6, IL-10 and IL-18 were unchanged. IRF5 and STAT6 were decreased, and PPARG was increased, independent of clinical response, and may represent a skew toward a PPARG-driven M2-like phenotype. IL1B expression was decreased in early clinical responders. A transient increase in STAT1, and a decrease in SOCS1 preceded the reduction in IL1B in early clinical responders. Changes in IL1B/STAT1/SOCS1 could be associated with crosstalk between IL-1 and IFN pathways in sJIA. These transcriptional changes might be useful as drug response biomarkers.

publication date

  • September 2018

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1016/j.clim.2018.06.005

PubMed ID

  • 29928998

Additional Document Info

start page

  • 9

end page

  • 18

volume

  • 194