Interferon-γ: Interleukin 4 ratios and associated type 1 cytokine expression in juvenile rheumatoid arthritis synovial tissue

Michael P. Scola, Susan D. Thompson, Hermine I. Brunner, Monica K. Tsoras, David Witte, Marc A. Van Dijk, Alexei A. Grom, Murray H. Passo, David N. Glass

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Objective. To compare synovial tissue cytokine mRNA expression between patients with juvenile rheumatoid arthritis (JRA) and a heterogeneous group of non-autoimmune arthropathies (controls) with respect to type 1/type 2 balance. Methods. Thirty-five JRA (average 9.1 years' disease duration) and 13 control synovial tissues were studied. As a measure of the type 1/type 2 cytokine balance in a subset of the JRA and control tissues, interferon-γ(IFN-γ) and interleukin 4 (IL-4) mRNA levels were measured by competitive fragment reverse transcription-polymerase chain reaction. To quantitate additional cytokines relevant to this balance, multiprobe ribonuclease protection assays were employed measuring IL-5, IL-10, IL-13, IL-15, IL-18, and IL-12 (p35 and p40 subunits). Immunohistochemistry was performed on JRA tissues using antibodies specific for IL-15 and IL-18. Results. A higher IFN-γ:IL-4 ratio (p = 0.034) was found in JRA tissues compared to controls. JRA tissues also displayed higher mRNA levels of IL-12p35 (p = 0.021), IL-15 (p = 0.002), and IL-18 (p = 0.017), but not IL-4 and IL-10. IFN-γ expression in JRA, but not controls, correlated strongly with IL-12p35 (r = 0.63) and IL-12p40 (r = 0.73) levels. A subset of IL-15+ and IL-18+ cells was detected in JRA synovial tissues, largely within perivascular aggregates. Conclusion. JRA synovial tissue cytokine expression patterns indicate a type 1 bias, even in the later stages of disease. The strong correlation between IFN-γ and IL-12 in JRA suggests a prominent role for IL-12 in promoting the type 1 bias, while IL-15 and IL-18 may also indirectly increase IFN-γ expression and further bias the immune response.

Original languageEnglish
Pages (from-to)369-378
Number of pages10
JournalJournal of Rheumatology
Volume29
Issue number2
StatePublished - 2002

Keywords

  • Interferon-γ
  • Interleukin 12
  • Interleukin 15
  • Interleukin 18
  • Juvenile rheumatoid arthritis
  • Synovial tissue

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

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