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

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Abstract
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 1β (IL‐1β) IL‐2, IL‐4, IL‐5, IL‐10, IL‐12, IL‐13, IL‐15, IL‐18, and for tumor necrosis factor α (TNFα) and interferon‐γ (IFNγ) were detected by reverse transcription–polymerase chain reaction of extracted RNA.Results: Nine of 10 nodules contained transcripts for IFNγ. We observed no evidence for the expression of IL‐2, IL‐4, or IL‐5 among the lymphokine genes analyzed. Transcripts for TNFα, IL‐1β, 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 IFNγ but not IL‐2, and prominent expression of IL‐1β and TNFα 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.