Clinical Evaluation of Collagen-Induced Arthritis in Female Lewis Rats: A Comprehensive Analysis of Disease Progression and Severity

Document Type : Original Article

Authors

1 Department of Applied Cell Sciences, Faculty of Basic Sciences and Advanced Medical Technologies, Royan Institute, ACECR, Tehran, Iran

2 Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran

3 Inotiv, Inc., West Lafayette, IN, USA

4 Advanced Therapy Medicinal Product Technology Development Center (ATMP-TDC), Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran

5 Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran

Abstract

Objective: The collagen-induced arthritis (CIA) model is the most commonly studied autoimmune model of rheumatoid
arthritis (RA). In this study, we investigated the usefulness of collagen type II emulsified in Freund's incomplete
adjuvant (CII/IFA) as a suitable method for establishing RA in Lewis rats. The aim of the present study was to present
a straightforward and effective method for inducing CIA in rats.
Materials and Methods: In this experimental study, animals were divided into two equal groups (n=5); control and
CIA. Five rats were injected intradermally at the base of the tail with a 0.2 ml CII/IFA emulsion. On the seventh day,
a 0.1 ml CII/IFA emulsion booster was injected. Arthritis symptoms that arose were evaluated at clinical, histological,
radiological, and at protein expression levels to find out if the disease had been induced successfully.
Results: Our finding showed a decreasing trend in the body weight during the RA induction period, while the arthritis
score and paw thickness were increased during this period. The results of the enzyme-linked immunosorbent assay
(ELISA) for serum samples revealed that the levels of proinflammatory cytokines, interleukin (IL)-1β, IL-6, IL-17, and
tumor necrosis factor (TNF)-α and anti-CII IgG were significantly increased in CIA rats compared to the control group.
After CIA induction, the level of anti-inflammatory protein IL-10 was decreased significantly. Radiographic examination
of the hind paws showed soft tissue swelling, bone erosion, and osteophyte formation in CIA rats. Additionally, based
on histological evaluations, the hind paws of the CIA group showed pannus formation, synovial hyperplasia, and bone
and cartilage destruction.
Conclusion: It seems that CII/IFA treatment can be an appropriate and effective method to induce RA disease in Lewis
rats. This well-established and well-characterized CIA model in female Lewis rats could be considered to study aspects
of RA and develop novel anti-arthritic agents.

Keywords

Main Subjects


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