Abnormal IL-1 receptor antagonist production in patients with polymyositis and dermatomyositis.
OBJECTIVE
To examine the relationship between serum levels of interleukin-1 receptor antagonist (IL-1Ra) and its gene expression in peripheral blood mononuclear cells (PBMC) from patients with polymyositis and dermatomyositis (PM/DM).


METHODS
IL-1Ra levels in sera from patients and supernatants of unstimulated monocyte cultures were measured by enzyme-linked immunosorbent assay. Expression of IL-1Ra mRNA was analyzed by Northern blotting, and an 86-base pair variable repeat polymorphism in intron 2 of the IL-1Ra gene was determined by polymerase chain reaction.


RESULTS
Serum IL-1Ra was significantly elevated in 27 patients with active-stage PM/DM when compared with levels in 16 patients with inactive-stage PM/DM and 19 normal controls. Serum concentrations of IL-1Ra were correlated with PM/DM disease activity. IL-1Ra mRNA was detected in freshly isolated PBMC from patients with active-stage PM/DM, but not in controls. Moreover, IL-1Ra concentrations were increased significantly in unstimulated monocytes from patients with active-stage PM/DM compared with monocytes from normal controls. However, there were no significant differences in IL-1Ra allele frequencies between patients and normal controls.


CONCLUSIONS
Elevation of both IL-1Ra mRNA and protein in sera of patients with active-stage PM/DM suggest that higher levels of serum IL-1Ra may reflect increased IL-1Ra production in myositis, and that IL-1Ra may regulate IL-1-mediated muscle fiber damage in PM/DM.
Son
K
K
First Department of Internal Medicine, Nihon University School of Medicine, Tokyo.
Tomita
Y
Y
Shimizu
T
T
Nishinarita
S
S
Sawada
S
S
Horie
T
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015152:Blotting, Northern; D003402:Creatine Kinase / Q000097:blood; D015342:DNA Probes / Q000737:chemistry; D003882:Dermatomyositis / Q000097:blood* / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005634:Fructose-Bisphosphate Aldolase / Q000097:blood; D015870:Gene Expression; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017285:Polymyositis / Q000097:blood* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D012795:Sialoglycoproteins / Q000097:blood* / Q000235:genetics*
D015415:Biomarkers; D015342:DNA Probes; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D003402:Creatine Kinase; D005634:Fructose-Bisphosphate Aldolase