Elevated serum interleukin 33 is associated with autoantibody production in patients with rheumatoid arthritis.
OBJECTIVE
Interleukin 33 (IL-33) is a novel cytokine involved in joint inflammation in animal models. We analyzed the expression of IL-33 in the serum and synovial fluid of patients with rheumatoid arthritis (RA) and investigated its possible pathophysiological importance.


METHODS
The concentration of IL-33 was measured by ELISA in the serum of 223 patients with RA and 159 controls. Anticyclic citrullinated peptide, rheumatoid factor (RF)-IgA, and RF-IgG were tested by ELISA. Antikeratin antibody and antiperinuclear factor were tested by indirect immunofluorescence assay. Erythrocyte sedimentation rate, C-reactive protein, and immunoglobulins were measured by standard laboratory techniques. The association of IL-33 level with clinical and serologic features of RA was analyzed. We tested the change of IL-33 level following tumor necrosis factor (TNF-α) blockade therapy in 40 patients with RA.


RESULTS
In contrast to almost no detectable IL-33 in osteoarthritis and healthy serum, IL-33 could be detected in 94 out of the 223 RA cases (42.2%). Serum IL-33 concentration was significantly higher in patients with RA than in control groups. The level of serum IL-33 decreased after anti-TNF treatment. The level of serum IL-33 was correlated with the production of IgM and RA-related autoantibodies including RF and anticitrullinated protein antibodies. However, no correlation was found between IL-33 concentration and acute-phase inflammation reactant or the score of the Disease Activity Index, suggesting a complex or indirect character of the link between IL-33 and the inflammation in RA.


CONCLUSIONS
The level of IL-33 is abnormally elevated in RA serum. The elevation of serum IL-33 was at least partly attributed to excessive TNF-α in RA. IL-33 might be involved in the regulation of autoantibody production in RA.
Mu
Rong
R
Department of Rheumatology and Immunology, People's Hospital, Peking University, Beijing, China.
Huang
He-Qing
HQ
Li
Yu-Hui
YH
Li
Chun
C
Ye
Hua
H
Li
Zhan-Guo
ZG
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000276:immunology* / Q000473:pathology; D001323:Autoantibodies / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D005260:Female; D006801:Humans; D000067596:Interleukin-33; D007378:Interleukins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
D001323:Autoantibodies; C506536:IL33 protein, human; D000067596:Interleukin-33; D007378:Interleukins