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

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...

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Bibliographic Details
Published in:Journal of rheumatology 2002-02, Vol.29 (2), p.369-378
Main Authors: SCOLA, Michael P, THOMPSON, Susan D, BRUNNER, Hermine I, TSORAS, Monica K, WITTE, David, VAN DIJK, Marc A, GROM, Alexei A, PASSO, Murray H, GLASS, David N
Format: Article
Language:English
Subjects:
Adolescent
Arthritis, Juvenile - metabolism
Arthritis, Juvenile - pathology
Biological and medical sciences
Child
Child, Preschool
Diseases of the osteoarticular system
Fluorescent Antibody Technique, Indirect
Humans
Immunohistochemistry
Infant
Inflammatory joint diseases
Interferon-gamma - genetics
Interferon-gamma - metabolism
Interleukin-12 - genetics
Interleukin-12 - metabolism
Interleukin-15 - genetics
Interleukin-15 - metabolism
Interleukin-18 - genetics
Interleukin-18 - metabolism
Interleukin-4 - genetics
Interleukin-4 - metabolism
Medical sciences
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - analysis
Synovial Membrane - metabolism
Synovial Membrane - pathology
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Summary: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-gamma (IFN-gamma) 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-gamma: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-gamma 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-gamma and IL-12 in JRA suggests a prominent role for IL-12 in promoting the type I bias, while IL-15 and IL-18 may also indirectly increase IFN-gamma expression and further bias the immune response.
ISSN:0315-162X
1499-2752