F. Handajani, S. Prabowo. Biomedical Engineering Vol.2 No.1 (2016) 1 Please cite this article as: Handajani, F, Prabowo S. Vitamin C inhibit upregulation of plasmaand joint interleukin-1β level in cold- stress exposed adjuvant arthritis. Biomed Eng (2016) IN PRESS BE BIOMEDICAL ENGINEERING journal homepage: be.ub.ac.id Vitamin C inhibit upregulation of plasma and joint interleukin-1β level in cold stress-exposed adjuvant arthritis Fitri Handajani 1† , Sulistiana Prabowo 1 1 Faculty of Medicine, Hang Tuah University, Surabaya, East Java, Indonesia A R T I C L E I N F O Article history: Received Accepted Available online Keywords: IL-1β Adjuvant arthritis Vitamin C Cold stress † Corresponding author: fitrihandajanidr@gmail.com A B S T R A C T 1. Introduction Rheumatoid arthritis (RA) is commom autoimmune disease characterized by chronic inflammatory process of synovial joints and subsequent progressive, erosive destruction of articular tissue. RA is associated with progressive disability, systemic complications, early death and socioeconomic costs [1-3]. RA affect 1 % of human population [2]. The etiology of RA remains unknown and the exact pathogenesis still obscure [2]. Interleukin-1β IL-1β play an important role in the pathogenesis of RA. Exacerbation and advancement of RA are associated with IL-1β upregulation [4]. Interleukin-1 (IL-1) has been implicated in the dysregulation of bone and cartilage remodelling characteristic of RA [3]. IL-1 acts directly on osteoclast increasing bone resorbing capacity and adversely affect cartilage remodelling [3]. Adjuvant arthritis is animal model of rheumatoid arthritis [5]. Cold stress cause increased body heat production by thermogenesis achieved by accelerating uncoupling oxidative phosphorylation in inner membrane of mitochondria. The energy generated is shunted from ATP synthesis to heat production. Increasing oxidative phosphorylation increases reactive oxygen species production (ROS) [6]. Nuclear Factor-kappaB (NF-B) is a key transcription factor regulating proinflammatory cytokines including IL-1β, involves in pathogenesis and progression of RA [7]. ROS triggers a cascade of events that activates NF-B and in turn upregulates IL-1β production. Vitamin C has antioxidant effect that may quench ROS produced by oxidative phosphorylations. We aimed to investigate whether cold stress increased plasma and joint IL-1β and whether vitamin C quenched ROS and reduced increased IL-1β. Objective: We aimed to investigate whether cold stress increased plasma and joint IL-1β and whether vitamin C quenched ROS and reduced increased IL-1β. Secondly whether there is any correlation between plasma and joint IL-1βlevel. Material and methods: Male adjuvant arthritic rats (age=10-12 weeks; n=8/group) were exposed to cold stress (5 o C for 15 minutes/day for 7 days) with/without vitamin C (50 mg/day orally) and then kept for 14 days. The control group did not receive either cold exposure or vitamin C. Plasma IL-1βlevel was measured using indirect ELISA and joint IL-1β was measured using imunohistochemistry before treatment, day 0, 7, 14 after treatment. Result: Cold stress significantly increased plasma IL-1β level directly after cold stress (p=0.025), 14 days after cold stress (p=0.002). Cold stress significantly increased percentage area positive of joint IL-1β day 7 (p=0.001), day 14 (p=0.001). Compared to controls vitamin C significantly reduced plasma and joint IL-1β directly after cold stress, day 7, 14 after cold stress (p< 0.05). No significant correlation between plasma and joint IL-1β in all groups (p>0.05). Conclusion: Cold stress increased plasma and joint IL-1β and vitamin C reduced increased IL-1β possibly by reducing ROS production and NF-B activation.