Study to low-dose interleukin-18 combined with interlukin-10 in early stage of mouse collagen Ⅱ -induced arthritis
10.3760/cma.j.issn.1007-7480.2010.06.008
- VernacularTitle:小剂量白细胞介素-18联合白细胞介素-10在早期Ⅱ型胶原诱导性关节炎中的作用研究
- Author:
Qiaomei DAI
;
Fengshan ZHANG
;
Yang LI
- Publication Type:Journal Article
- Keywords:
Interleukin-18;
Interleukin-10;
Arthritis,experimental
- From:
Chinese Journal of Rheumatology
2010;14(6):388-390,后插一
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of exogenous murine interleukin-18 (IL-18) on early mouse collagen Ⅱ -induced arthritis (CIA). Methods Mice were injected intraperitoneallg IL-18 (0.2 μg/d) combination with IL-10 (0.1 μg/d), IL-4 (0.1 μg/d) and IL-12 (0.1 μg/d) daily for five days before the onset of CIA. The arthritis response was monitored visually by macroscopic scoring. Reverse transcription -polymerase chain reaction (RT-PCR) was employed to determine the mRNA expression of cytokine in patella with adjacent synovium in CIA mouse. Histology of knee was examined to assess the occurrence of cartilage destruction and bone erosion. Wilcoxon rank test was selected. Results IL-18/IL-4 treatment could slightly suppress the macroscopic score of arthritis, but a more pronounced amelioration was found in mice treated with the combination of IL-18 and IL-10 during early treatment. On 38 days after immunizatian macroscopic score in treated group (0.12±0.20) was significantly improves than in the control group (0.29±0.19, P<0.05). This resulted in both the suppression of macroscopic signs of inflammation and the reduction of cellular infiltrates in the synovial tissue, which provided the protection against cartilage destruction. Moreover, the expression of Thl cytokines [IL-18 (0.22±0.06), IL-12 (0.14±0.05)] and inflammatory cytokine [IL-6 (0.22±0.11)] was greatly inhibited both in the synovial tissue and in the articular cartilage in the treatment groups compared with those in the control groups (P<0.05). However, the mRNA levels of Th2 cytokines [IL-10 (6.35±0.12), IL-4 (3.57±0.13)] were up-regulated after IL-18/IL-10 treatment (P<0.05). Moreover, IL-18R (0.40±0.15) levels were down-regulated compared with those in the control group (P<0.05). T-bet mRNA levels were decreased in IL-18/IL-10 compared with the control group, and GATA-3 mRNA (5.71±0.11) levels were significantly higher than those in the control group (P<0.05). Conclusion Low dose IL-18/IL-10 treatment can inhibit Th1 cytokines expression and induce Th2 cytokines expression, which may be mediated not only by inhibiting Th1 responses through IL-18/IL-18R mechanism, but also by inducing anti-inflammatory mediators such as IL-10 and IL-4 through a GATA-3-dependent mechanism.
