Increased levels of interleukin 33 in sera and synovial fluid from patients with active rheumatoid arthritis.
OBJECTIVE
To determine levels of interleukin 33 (IL-33) in serum and synovial fluid (SF) and their clinical associations in patients with rheumatoid arthritis (RA). To evaluate the ability of activated peripheral blood mononuclear cells (PBMC) and fibroblast-like synoviocytes (FLS) from RA patients to release IL-33.


METHODS
Sera were obtained from 59 patients with RA, 10 patients with infectious diseases, and 42 healthy volunteers. SF samples were obtained from 15 patients with RA and 13 with osteoarthritis. IL-33 levels were measured using a sandwich ELISA after removal of rheumatoid factor with protein A-Sepharose beads. FLS were stimulated with IL-1beta and tumor necrosis factor, and treated with or without chemical damage. PBMC were stimulated with anti-CD3/CD28 antibodies. The levels of IL-33 were measured in the culture supernatants and cell lysates by ELISA or immunoblotting.


RESULTS
Serum IL-33 levels were significantly higher in RA patients, especially in the high disease activity group compared to the moderate or low activity group. IL-33 levels in SF were elevated in all 15 RA patients measured. IL-33 levels were higher in SF samples than in sera in 7 RA patients measured simultaneously. The 30-kDa IL-33 precursor was detected in the culture supernatants of damaged FLS but was not detected in those of activated PBMC and non-damaged FLS.


CONCLUSIONS
IL-33 levels were elevated in sera and SF samples from patients with RA, and correlated with disease activity. IL-33 was produced mainly in inflamed joints; IL-33/ST2L signaling might play an important role in joint inflammation of human RA.
Matsuyama
Yasushi
Y
Division of Rheumatology and Clinical Immunology and Department of Biochemistry, Jichi Medical University, Tochigi, Japan.
Okazaki
Hitoaki
H
Tamemoto
Hiroyuki
H
Kimura
Hirotaka
H
Kamata
Yasuyuki
Y
Nagatani
Katsuya
K
Nagashima
Takao
T
Hayakawa
Morisada
M
Iwamoto
Masahiro
M
Yoshio
Taku
T
Tominaga
Shin-ichi
S
Minota
Seiji
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D000067596:Interleukin-33; D007378:Interleukins / Q000378:metabolism*; D007596:Joints / Q000276:immunology / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D008875:Middle Aged; D015398:Signal Transduction / Q000502:physiology; D013582:Synovial Fluid / Q000276:immunology*
D018501:Antirheumatic Agents; C506536:IL33 protein, human; D000067596:Interleukin-33; D007378:Interleukins