Interleukin-18 : expression in ra synovial tissue and its contribution to interferon-y production by synovial t-cells

Abstract EN

Objective : to investigate the expression and function of interleukin-18 (IL-18) protein in synovial tissue (ST) of patients with rheumatoid arthritis (RA).

Methodology : IL-18 and IL-18 receptors (IL-18R) mRNA expression was detected by reverse transcription-polymerase chain reaction (RT-PCR).

Expression of IL-18 at protein level was analyzed by western plotting technique.

Cytokines ; (IL-18 and interferon-γ [IFN-γ]) in culture supernatants from ST cell organ and synovial cultures were measured by ELISA.

Samples : the ST samples were taken from 29 RA patients and 23 osteoarthritis patients (OA) were included as controls.

Results : Using RT-PCR, for RAST and OAST, mRNA expression of IL-18 was detected in 26 out of 29 (89.7 %) RA patients and in 11 out of 23 (47.8 %) OA controls.

However, mRNA expression of IL-18 R α and βchains were detected in 26 and 24 out of 29 (89.7 % and 82.8 %) RA patients, respectively.

OAST did not express mRNA of α and β chains of IL-18 R.

In vitro study of IL-18 production by ST showed significantly higher levels in RA compared to that of OA patients (p < 0.005).

Western blotting revealed that RAST expressed IL-18 more abundantly than OAST (p < 0.02).

Only IL-12, but not IL-18, stimulates IFN -γ production by RAST cells [M ± SD = 230 ±1 7 pg / ml].

However, when IL-12 was combined with IL-18, they could significantly stimulate IFN -γ production by RAST cells [M ± SD = 612 ± 35 pg / ml].

OAST cells did not respond to neither to IL-12 alone nor when combined to IL-18.

Conclusion : IL-18 is expressed in RA synovia and contributes to the production of IFN -γ by the infiltrating T-cells.

These cytokines could play a role in the synovial inflammation in RA patients.