Pathogenic mechanisms in the rheumatoid nodule: comparison of proinflammatory cytokine production and cell adhesion molecule expression in rheumatoid nodules and synovial membranes from the same patient.
OBJECTIVE
To investigate the production of proinflammatory cytokines and expression of cell adhesion molecules in the rheumatoid nodule.


METHODS
Cytokine content (tumor necrosis factor alpha [TNFalpha], interleukin-1beta [IL-1beta], and IL-1 receptor antagonist [IL-1Ra]), at the messenger RNA (mRNA) and protein levels, and cell adhesion molecule expression were studied in 16 rheumatoid nodules and 6 synovial membranes.


RESULTS
Macrophages in the rheumatoid nodules contained TNFalpha, IL-1beta, and IL-1Ra mRNA and protein, particularly in perivascular cells of the stroma and in the palisading layer. All cell adhesion molecules studied were expressed in both the rheumatoid nodules and synovial membranes, with increased expression of E-selectin in the rheumatoid nodule compared with the synovial membrane, and with the absence of vascular cell adhesion molecule 1 expression on cells of the palisading layer in the rheumatoid nodule.


CONCLUSIONS
The presence of similar proinflammatory cytokines and cell adhesion molecules in the rheumatoid nodule and synovial membrane suggests that similar pathogenic processes result in the chronic inflammation and tissue destruction in these lesions.
University of Otago Medical School, Dunedin, New Zealand.
R
R
Wikaningrum
J
J
Highton
A
A
Parker
M
M
Coleman
P A
PA
Hessian
P J
PJ
Roberts-Thompson
M J
MJ
Ahern
M D
MD
Smith
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis; D008264:Macrophages / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors; D012218:Rheumatoid Nodule / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000235:genetics; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015815:Cell Adhesion Molecules; D016207:Cytokines; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha