Cytokine profile of the rheumatoid nodule suggests that it is a Th1 granuloma

Arthritis Rheum. 2003 Feb;48(2):334-8. doi: 10.1002/art.10776.


Objective: To define the cytokine profile within rheumatoid subcutaneous nodules, and to determine whether the destructive inflammatory process in this lesion displays features of a lymphocyte-driven Th1 or Th2 granuloma.

Methods: Subcutaneous nodules excised from 10 patients with rheumatoid arthritis were examined. Transcripts for interleukin 1beta (IL-1beta) IL-2, IL-4, IL-5, IL-10, IL-12, IL-13, IL-15, IL-18, and for tumor necrosis factor alpha (TNFalpha) and interferon-gamma (IFNgamma) were detected by reverse transcription-polymerase chain reaction of extracted RNA.

Results: Nine of 10 nodules contained transcripts for IFNgamma. We observed no evidence for the expression of IL-2, IL-4, or IL-5 among the lymphokine genes analyzed. Transcripts for TNFalpha, IL-1beta, IL-10, IL-15, and IL-18 were present in all 10 nodules. Transcripts for IL-12 were present in all but one nodule. Expression of IL-13 messenger RNA was observed in only 5 nodules.

Conclusion: The cytokine profile within the rheumatoid nodule (i.e., presence of IFNgamma but not IL-2, and prominent expression of IL-1beta and TNFalpha together with IL-12, IL-18, IL-15, and IL-10) is similar to the profile of cytokines in the synovial lesion of rheumatoid arthritis, which is generally accepted as being attributable to a Th1-mediated inflammatory mechanism. Our results suggest that damage to affected synovial membrane or subcutaneous tissue is caused by the same inflammatory mechanisms, and that the nodule is a Th1 granuloma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antirheumatic Agents / adverse effects
  • Cytokines / genetics*
  • Female
  • Gene Expression / immunology
  • Granuloma / chemically induced
  • Granuloma / immunology
  • Granuloma / pathology
  • Humans
  • Interferon-gamma / genetics
  • Interleukin-1 / genetics
  • Interleukin-10 / genetics
  • Interleukin-12 / genetics
  • Interleukin-13 / genetics
  • Interleukin-15 / genetics
  • Interleukin-18 / genetics
  • Male
  • Methotrexate / adverse effects
  • Middle Aged
  • RNA, Messenger / analysis
  • Rheumatoid Nodule / chemically induced
  • Rheumatoid Nodule / immunology*
  • Rheumatoid Nodule / pathology*
  • Th1 Cells / immunology*
  • Th1 Cells / pathology*
  • Tumor Necrosis Factor-alpha / genetics


  • Antirheumatic Agents
  • Cytokines
  • Interleukin-1
  • Interleukin-13
  • Interleukin-15
  • Interleukin-18
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-12
  • Interferon-gamma
  • Methotrexate