Interleukin-1 in monocyte activation phenotypes in systemic juvenile idiopathic arthritis

Observations from a clinical trial of rilonacept, an interleukin-1 inhibitor

Yujuan Zhang, Saloni Gupta, Alexandra Ilstad-Minnihan, Sashi Ayyangar, Arielle D. Hay, Virginia Pascual, Norman Todd Ilowite, Claudia Macaubas, Elizabeth D. Mellins

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)9-18
Number of pages10
JournalClinical Immunology
Volume194
DOIs
StatePublished - Sep 1 2018

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Juvenile Arthritis
Interleukin-1
Monocytes
Clinical Trials
Phenotype
Pharmacological Biomarkers
Interleukin 1 Receptor Antagonist Protein
Interleukin-18
Rheumatic Diseases
Serum
Innate Immunity
Interleukin-10
Interleukin-6
Transcription Factors
Pathology
Cytokines
Gene Expression
Polymerase Chain Reaction
rilonacept
Therapeutics

Keywords

  • Juvenile arthritis
  • Monocytes;cytokine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Interleukin-1 in monocyte activation phenotypes in systemic juvenile idiopathic arthritis : Observations from a clinical trial of rilonacept, an interleukin-1 inhibitor. / Zhang, Yujuan; Gupta, Saloni; Ilstad-Minnihan, Alexandra; Ayyangar, Sashi; Hay, Arielle D.; Pascual, Virginia; Ilowite, Norman Todd; Macaubas, Claudia; Mellins, Elizabeth D.

In: Clinical Immunology, Vol. 194, 01.09.2018, p. 9-18.

Research output: Contribution to journalArticle

Zhang, Yujuan ; Gupta, Saloni ; Ilstad-Minnihan, Alexandra ; Ayyangar, Sashi ; Hay, Arielle D. ; Pascual, Virginia ; Ilowite, Norman Todd ; Macaubas, Claudia ; Mellins, Elizabeth D. / Interleukin-1 in monocyte activation phenotypes in systemic juvenile idiopathic arthritis : Observations from a clinical trial of rilonacept, an interleukin-1 inhibitor. In: Clinical Immunology. 2018 ; Vol. 194. pp. 9-18.
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