In vivo gene expression of type 1 and type 2 cytokines in synovial tissues from patients in early stages of rheumatoid, reactive, and undifferentiated arthritis

S. Kotake, Jr Schumacher, C. H. Yarboro, T. K. Arayssi, J. A. Pando, K. S. Kanik, M. F. Gourley, J. H. Klippel, R. L. Wilder

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Abstract

It has been reported that the mRNA of the type 1 cytokine, interferon- gamma (IFN-γ)-but not the type 2 cytokine interleukin-4 (IL-4)-is detected in synovial tissues of rheumatoid arthritis (RA) patients, whereas both IFN- γ and IL-4 mRNA are detected in reactive arthritis (ReA). To evaluate such data more extensively, we obtained 208 synovial specimens in a prospective study of 52 early synovitis patients (13 RA, 11 ReA, 28 undifferentiated oligoarthropathy) and analyzed type I and type 2 cytokine mRNA expression in specimens containing sufficient mRNA. Using a nested reverse transcriptase polymerase chain reaction technique, we measured the relative mRNA levels of 10 cytokines and CD3 δ chain. We detected IL-10, IL-15, and CD3 δ chain mRNA in all RA and ReA patients and frequently detected tumor necrosis factor-α, IL-1β, and IFN-γ mRNA. IL-6 and IL-12 p40 mRNA were detected in approximately one-half of the patients. We also detected greater amounts of IL-2 and IFN-γ mRNA in ReA than were detected in RA. However, we rarely detected IL-4 or IL-13 mRNA. Similar cytokine profiles were observed in undifferentiated oligoarthropathy. The amounts of cytokine mRNAs, except for IL-10, in specimens from the patients taking prednisone or second-line antirheumatic drugs tended to be less than in specimens from the patients taking neither prednisone nor second-line antirheumatic drags. These results suggest that cytokine mRNA profiles in patients with RA, ReA, and undifferentiated arthritis in their early stages are skewed toward proinflammatory macrophage-derived and type 1 cytokines, IL-10-not IL-4 or IL-13-mRNA appears to be the major anti-inflammatory cytokine mRNA. Drug therapy is associated with depressed proinflammatory and type 1 cytokine mRNA production. The differences in the expression of IL-2 and IFN-γ mRNA between RA and ReA may reflect unique etiological or host factors associated with the early stages of these diseases.

Original languageEnglish
Pages (from-to)286-302
Number of pages17
JournalProceedings of the Association of American Physicians
Volume109
Issue number3
Publication statusPublished - 28 May 1997

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Keywords

  • Chlamydia trachomatis
  • Type 1 helper T cell
  • Type 2 helper T cell
  • interleukin-15
  • nested RT-PCR

ASJC Scopus subject areas

  • Medicine(all)

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