Biologic Therapy in Rheumatoid Arthritis / 한양의대학술지

Rheumatoid arthritis (RA) is a common autoimmune disease of unknown etiology characterized by symmetric and erosive synovitis. The course of RA is usually chronic and progressive, so it can result destructive joint damages. Nonsteroidal anti-inflammatory drugs, disease modifying anti-rheumatic drugs (DM ARDs) and low-dose corticosteroid have been used for the treatments of RA. The importance of early usage of DMARDs are stressed recently, however, the effects of DMARDs on long-term prognosis is not convincing. Since 1998, several biologic agents were developed for RA and showed promising results. These agents include TNF-alpha blockers such as etanercept, infliximab, adalimumab, and IL-1 receptor antagonist such as anakinra. Clinical studies for rituximab, anti-IL-6 receptor monoclonal antibody, and CTLA4-Ig are underway. The biologic agents show rapid improvement in clinical and laboratory parameters and may prevent the erosions on Xray, but because of costs and unknown long-term side effects, we should be more careful for using these drugs.

Effects of the EL-1 Receptor Antagonist on Matrix Metalloproteinase 1 Expression in UV-irradiated Fibroblasts / 中华皮肤科杂志

Objective To study the effects of the IL-1 receptor antagonist (IL-1Ra) on matrix metalloproteinase 1 (MMP-1) expression in UV-irradiated fibroblasts. Methods Simulating the impact of environmental ultraviolet (UV) light on human skin, UVA-irradiated human fibroblasts were cultured in medium obtained from UVB-irradiated HaCaT cells. MMP-1 was detected by ELISA in the culture medium of fibroblasts. After treatment with IL-1Ra, the mRNA expression levels of C-Jun, C-Fos and GAPDH (internal control) of fibroblasts were measured by real-time fluorescent quantitative RT-PCR. Results Production of MMP-1 by UVA (10 J/cm2)-irradiated fibroblasts was increased in culture medium from UVB-irradiated HaCaT cells. The fibroblasts produced significantly higher levels of MMP-1 in culture medium from HaCaT cells treated without UVB than those with 15 mJ/cm2 UVB (t = 8.413,P= 0.014). However, IL-1Ra inhibited MMP-1 production of fibroblasts in a dose-dependent manner. Standard curves of real-time fluorescent quantitative RT-PCR showed a linear correlation between the copy number and the threshold cycle (Tc). Melting curves confirmed the specificity of PCR products. The original copy numbers of C-Jun and C-Fos as well as the ratios of the numbers to the GAPDH copy number showed that IL-1Ra inhibited the C-Jun mRNA expression of fibroblasts in a dose-dependent manner but had no significant effects on C-Fos mRNA expression. Conclusions The culture medium from UVB-irradiated HaCaT cells can promote MMP-1 production by UVA-irradiated fibroblasts. IL-1Ra reduces MMP-1 production via inhibition of C-Jun mRNA expression.

Polymorphism in the IL-1 Receptor Antagonist Gene in Vitiligo

BACKGROUND: The severity of several chronic inflammatory diseases was reported to be associated with polymorphism of the IL-1 receptor antagonist gene(IL-lrn). OBJECTIVE: This study was performed to study the polymorphism of the IL-1rn in vitiligo and in the normal Korean population. METHODS: Thirty one cases of vitiligo and seventy nine normal Koreans as control were studied for the polymorphism of IL-1 rn. RESULTS: The frequency of allele 2 of the IL- I rn in 31 patients with vitiligo was compared with that of the 79 healthy controls. The frequency of allele 2 was 1.6% in vitiligo patients and 3.8% in the normal controls. CONCLUSION: There was no significant difference in the frequency of allele 2 between the vitiligo patients and normal controls.