Synovial interleukin-1 receptor antagonist and interleukin-1 balance in rheumatoid arthritis.
OBJECTIVE
To quantify interleukin-1 receptor antagonist (IL-1ra) and IL-1 production and gene expression by rheumatoid arthritis (RA) synovial tissue (ST) cells.


METHODS
IL-1 alpha, IL-1 beta, and IL-1ra protein levels were measured by enzyme-linked immunosorbent assay in fresh and cultured ST cells, purified synovial macrophages, and fibroblast-like synoviocytes (FLS). The relative expression of the secreted form of IL-1ra (sIL-1ra) and the alternatively spliced intracellular form (icIL-1ra) was determined by reverse transcription polymerase chain reaction (RT-PCR) techniques.


RESULTS
IL-1 alpha, IL-1 beta, and IL-1ra were present in fresh and cultured ST cell samples of synovium from RA and osteoarthritis patients. IL-1ra:IL-1 ratios ranged from 1.2 to 3.6, which is below the 10-100-fold excess of IL-1ra needed to inhibit IL-1 bioactivity. Isolated CD14+ synovial macrophages secreted IL-1ra, but the amount was much less than that of alveolar or in vitro-derived macrophages. Cultured FLS contained intracellular IL-1ra but secreted little IL-1ra into the culture supernatants. RT-PCR showed that icIL-1ra mRNA was more abundant than sIL-1ra mRNA in FLS and unfractionated ST cells.


CONCLUSIONS
IL-1ra production by RA ST cells is deficient relative to total production of IL-1.
Firestein
G S
GS
University of California, San Diego Medical Center.
Boyle
D L
DL
Yu
C
C
Paine
M M
MM
Whisenand
T D
TD
Zvaifler
N J
NJ
Arend
W P
WP
D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology; D001483:Base Sequence; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D006801:Humans; D007118:Immunoassay; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D008969:Molecular Sequence Data; D010003:Osteoarthritis / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D013583:Synovial Membrane / Q000737:chemistry* / Q000276:immunology
D007375:Interleukin-1; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1