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


CONCLUSIONS
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.
Hessian
Paul A
PA
Otago Medical School, University of Otago, Dunedin, New Zealand.
Highton
John
J
Kean
Annabel
A
Sun
Cheuk Kwan
CK
Chin
Michael
M
D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects; D016207:Cytokines / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000276:immunology; D006099:Granuloma / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D018664:Interleukin-12 / Q000235:genetics; D018793:Interleukin-13 / Q000235:genetics; D019409:Interleukin-15 / Q000235:genetics; D020382:Interleukin-18 / Q000235:genetics; D008297:Male; D008727:Methotrexate / Q000009:adverse effects; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D012218:Rheumatoid Nodule / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology*; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D018501:Antirheumatic Agents; D016207:Cytokines; D007375:Interleukin-1; D018793:Interleukin-13; D019409:Interleukin-15; D020382:Interleukin-18; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; D008727:Methotrexate