Mature form of interleukin 18 is expressed in rheumatoid arthritis synovial tissue and contributes to interferon-gamma production by synovial T cells.
OBJECTIVE
To investigate the expression and function of interleukin 18 (IL-18) in synovial tissue (ST) of patients with rheumatoid arthritis (RA).


METHODS
The localization of IL-18 in ST was analyzed by immunohistochemistry. IL-18 and IL-18 receptor (IL-18R) mRNA were detected by RT-PCR. Expression of IL-18 at the protein level was analyzed by Western blotting. Cytokines in culture supernatants were measured by ELISA.


RESULTS
From immunohistochemical analysis, IL-18-producing cells were localized in the lining layer and sublining region of RA ST. Most of them coexpressed CD68 antigen. In ST from patients with osteoarthritis (OA), IL-18-producing cells were localized only in the sublining region and the numbers of these cells were small. From RT-PCR, RA ST expressed mRNA of IL-18, as well as alpha- and beta-chains of IL-18R. OA ST did not express or very weakly expressed mRNA of alpha- and beta-chains of IL-18R. ST from RA patients produced significantly larger amounts of IL-18 in vitro than OA ST. Western blotting revealed that RA ST expressed mature IL-18 more abundantly than OA ST. IL-12 alone stimulates interferon-gamma (IFN-gamma) production by RA synovial tissue cells, but IL-18 alone could not. In the presence of IL-12, however, IL-18 could synergistically stimulate IFN-gamma production by RA synovial tissue cells. OA synovial tissue cells responded to neither IL-12 nor IL-12 + IL-18. IL-18 showed synergistic effects with IL-12 on promoting the ability of synovial T cells from RA patients to produce IFN-gamma.


CONCLUSIONS
These findings suggest that mature IL-18 is expressed in RA synovia and contributes to the production of IFN-gamma by infiltrating T cells.
Tanaka
M
M
Institute of Rheumatology, Tokyo Women's Medical University, Japan.
Harigai
M
M
Kawaguchi
Y
Y
Ohta
S
S
Sugiura
T
T
Takagi
K
K
Ohsako-Higami
S
S
Fukasawa
C
C
Hara
M
M
Kamatani
N
N
D001172:Arthritis, Rheumatoid / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology / Q000494:pharmacology; D020382:Interleukin-18 / Q000235:genetics* / Q000494:pharmacology; D053727:Interleukin-18 Receptor alpha Subunit; D009924:Organ Culture Techniques; D010003:Osteoarthritis / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D018123:Receptors, Interleukin / Q000235:genetics; D053724:Receptors, Interleukin-18; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*
C508572:IL18R1 protein, human; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18; D018664:Interleukin-12; D007371:Interferon-gamma