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PMID: 10733472 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Differential Th1/Th2 cytokine patterns in chronic arthritis: interferon gamma is highly expressed in synovium of rheumatoid arthritis compared with seronegative spondyloarthropathies.

Annals of the rheumatic diseases ·Vol. 59 ·No. 4 ·2000-04-00 ·Pages 263-8

Cañete JD, Martínez SE, Farrés J, Sanmartí R, Blay M, Gómez A, Salvador G, Muñoz-Gómez J

Abstract

To investigate possible differences in Th1 and Th2 cytokine mRNA expression in the synovial tissue (ST) of patients with rheumatoid arthritis (RA) and seronegative spondyloarthropathies (SpA) with diagnostic and/or pathogenic interest. Eleven RA patients and 14 SpA patients (10 with undifferentiated spondyloarthropathy (USpA), two with ankylosing spondylitis (AS) and two with psoriatic arthritis (PsA)) were included. Th1 (interferon gamma, interleukin 2) and Th2 (interleukin 4, interleukin 5 and interleukin 10) cytokine mRNA levels from arthritic knee ST were quantified by using an optimised polymerase chain reaction method with a computerised analysis system. Protein levels of proinflammatory cytokines (interleukin 1, tumour necrosis factor alpha and interleukin 6) in synovial fluid were quantified with a specific ELISA test. Th1 cytokines were detected in all of RA ST samples in contrast with 58% (interferon gamma) and 71% (interleukin 2) of SpA samples. Th2 cytokines were expressed in 90% of RA ST samples, but the findings in SpA were interleukin 10 in 90%, interleukin 4 in 60% and interleukin 5 in 40% of ST samples. However, when the mRNA levels of each cytokine were quantified and corrected for T cell mRNA levels, only interferon gamma levels were significantly higher in RA than in SpA (p<0.003). Thus, the Th1/Th2 cytokine ratio in RA was fivefold that of SpA. Synovial fluid interleukin 1beta concentrations were higher in RA than in SpA (p<0. 05); there were also higher synovial fluid levels of tumour necrosis factor alpha in RA than in SpA, but without statistical significance. This study has detected both Th1 and Th2 cytokine gene expression in ST from RA and SpA patients. Synovium interferon gamma mRNA levels and SF interleukin 1beta protein levels were significantly higher in RA than in SpA, so reflecting the known proinflammatory activity of interferon gamma through macrophage activation. Thus, the Th1 (interferon gamma)/Th2 (interleukin 4) ratio is significantly higher in RA than in SpA ST. These data confirm previous studies on ST Th1/Th2 balance in RA and extend previous work in comparing ST RA with subgroups of SpA distinct of ReA.

MeSH Terms
Adult Aged Arthritis, Psoriatic/immunology Arthritis, Rheumatoid/immunology Cytokines/genetics,metabolism Female Humans Interferon-gamma/metabolism Male Middle Aged Prohibitins RNA, Messenger/genetics Reverse Transcriptase Polymerase Chain Reaction Spondylitis/immunology Spondylitis, Ankylosing/immunology Synovial Fluid/immunology Th1 Cells/immunology Th2 Cells/immunology
Chemicals
Cytokines PHB2 protein, human Prohibitins RNA, Messenger Interferon-gamma
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Cañete J D
Department of Rheumatology, Hospital Clinic de Barcelona, Villarroel 170, 08036, Barcelona, Spain.
Martínez S E
Farrés J
Sanmartí R
Blay M
Gómez A
Salvador G
Muñoz-Gómez J
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Article Info
Journal
Annals of the rheumatic diseases
Abbr.
Ann Rheum Dis
ISSN
0003-4967
Published
2000-04-00
Pages
263-8
Language
English
Region
England
NLM ID
0372355
PMCID
PMC1753106
Subset
IM
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