Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Local Expression of IL-27 Reduces Collagen Induced Arthritis through Reduction of Monocyte Migration and Vascularization.
Pickens4, Sarah R., Volin1, Michael V., Mandelin2, Arthur M., Shahrara3, Shiva
To determine the effect and potential mechanism of IL-27 treatment in rheumatoid arthritis (RA), local expression of IL-27 was studied in ankle joints of collagen induced arthritis (CIA) mice compared to control animals.
Adenovirus containing IL-27 transcript (Ad-IL-27) was constructed and was locally delivered into the ankles of CIA mice. Clinical parameters were assessed histologically and by measuring ankle circumference. IL-17 and its downstream targets, as well as cytokines promoting TH-17 cell differentiation, were quantified by ELISA from CIA tissue homogenates locally expressing IL-27 or Ad-control. Ankles from both treatment groups were immunostained for neutrophil and monocyte abundance and vascularization was determined by quantifying ankle hemoglobin levels and PECAM expression by real-time RT-PCR.
The joint circumference of Ad-IL-27 injected animals was significantly smaller than control animals throughout the study. Histological analysis of ankles from day 41 confirmed that local expression of IL-27 resulted in significantly less inflammation compared to the control group. Further histological studies demonstrated that local expression of IL-27 resulted in a significant decrease (p<0.05) of synovial lining thickness and bone erosion. Next, we found that the cytokines which induce TH-17 cell differentiation (IL-1b and IL-6) and the downstream targets of IL-17 (CXCL1, CXCL5 and CCL2) were significantly decreased in ankle homogenates by local expression of IL-27 compared to control treatment. CIA ankles immunostained for neutrophils and monocytes showed that the local expression of IL-27 greatly decreased the infiltration of these cells into the ankle joints compared to control group. In order to quantify the vascularization changes in the Ad-IL-27 group, ankle hemoglobin and PECAM levels were quantified and compared to control group. Ad-IL-27 treated CIA ankle joints had significantly reduced hemoglobin and PECAM levels compared to control joints.
Our results suggest that increased IL-27 levels relieved arthritis in CIA ankles. This amelioration of arthritis involved a reduction of IL-714-induced TH-17 cell differentiation and resulted in decreased IL-714-mediated monocyte recruitment and angiogenesis. Hence, IL-27 may be a therapeutic target in RA.
To cite this abstract, please use the following information:
Pickens, Sarah R., Volin, Michael V., Mandelin, Arthur M., Shahrara, Shiva; Local Expression of IL-27 Reduces Collagen Induced Arthritis through Reduction of Monocyte Migration and Vascularization. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :714