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Open Access Relationships between Cytokine Levels and Disease Parameters during the Development of a Collagen-induced Arthritis Model in Cynomolgus Macaques (Macaca fascicularis)

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In rheumatoid arthritis research, NHP models of collagen-induced arthritis are important because these species share many immunologic and pathologic features with humans. In addition, serum levels of various cytokines in patients with rheumatoid arthritis have been studied as immune markers for disease prediction, early diagnosis, and effective therapeutic management. The purpose of this study was to identify changes in cytokine levels that occur during the development of collagen-induced arthritis in female cynomolgus macaques (n = 8) and to assess the relationships between these changes and various disease parameters. Blood samples were collected weekly before (week 0) and after (weeks 1 through 7) immunization with type II collagen; clinicopathologic and cytokine data from those samples and other clinical parameters were used in correlation analysis. Serum levels of IFN γ, chemokine (C-C motif) ligand 2 (CCL2), and IL6 showed significant changes after generation of collagen-induced arthritis. IFNγ levels showed a strong negative correlation with body weight (an indicator of general body condition), and CCL2 and IL6 showed moderate negative correlation with body weight. Serum IL6 levels showed moderate positive correlation with the soft tissue swelling score and strong positive correlation with serum C-reactive protein levels in our NHP model of collagen-induced arthritis. In addition, serum levels of matrix metalloproteinase 3 increased significantly after inoculation with type II collagen and showed a moderate positive correlation with serum levels of C-reactive protein, IL6, and IL15. These results suggest close correlations between various cytokines and disease parameters in NHP models of rheumatoid arthritis. These cytokines therefore potentially could be used as markers for monitoring the efficacy of novel treatments in NHP models of rheumatoid arthritis.

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Document Type: Miscellaneous

Affiliations: 1: Department of Veterinary Clinical Pathology, College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon, Republic of Korea 2: Department of Surgery, Division of Transplantation, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, and GenNBio, Seoul, Republic of Korea

Publication date: June 1, 2019

This article was made available online on May 29, 2019 as a Fast Track article with title: "Relationships between Cytokine Levels and Disease Parameters during the Development of a Collagen-induced Arthritis Model in Cynomolgus Macaques (Macaca fascicularis)".

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  • Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.

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