Session Title: Rheumatoid Arthritis: Animal Models
Session Type: Abstract Submissions (ACR)
Background/Purpose: Steroids are the main therapy for chronic inflammatory diseases. They are very effective, but induce many side effects, such as osteoporosis, making it important that the dose steroids be reduced. However, some patients with chronic inflammatory disease may have difficulty tapering off steroids. It is thought that IL-6 might be involved in the steroid effects because elevated levels of IL-6 are found in these patients. Here, we elucidated the role of IL-6 in several effects of steroids using a collagen-induced arthritis (CIA) mouse model to examine the possibility of combination therapy.
Methods: To prepare a CIA model, DBA/1J mice were immunized intradermally with bovine type II collagen, and 21 days later (Day 21) once again given a booster injection. Mice were treated with the steroid prednisolone (PSL) intraperitoneally from Day 21 at doses of 1, 3, and 6 mg/kg five times a week or were administered with 8 mg of rat anti-mouse IL-6R monoclonal antibody (MR16-1) intraperitoneally once on Day 21. Another group was given a combination of the two from Day 21. Clinical symptoms of arthritis were evaluated by observation and expressed as an arthritis score on a scale of 0–4 for each limb. To assess the side effects of PSL, BMD was measured with DXA, and neutrophils and lymphocytes were quantified in blood using a sysmex system. Furthermore, synovial cells from CIA mice were cultured in the presence of dexamethasone (DEX) for 3 h after IL-6 pretreatment, and then COXII mRNA was quantified by real-time PCR.
Results: PSL dose-dependently reduced the arthritis score in the CIA model on the peak (Day 33) of arthritis. At the same time, neutrophil count was increased and lymphocyte count was decreased in a dose-dependent manner. MR16-1 in combination with low doses of PSL (1, 3 mg/kg) improved clinical symptoms significantly more than the same dose of PSL alone on Day 33 even though administration of MR16-1 alone resulted in no improvement. Interestingly, neutrophil and lymphocyte counts did not change and BMD was not reduced. To explore how MR16-1 could improve the anti-inflammatory effect of PSL, we next examined the influence of IL-6 on DEX activity in vitro. COXII expression was clearly suppressed by DEX, but IL-6 pretreatment attenuated the inhibitory effect of DEX.
Conclusion: We demonstrated that IL-6 blockade augmented the anti-inflammatory effect of PSL without changing BMD or neutrophil and lymphocyte counts in CIA mice. IL-6 blockade might make steroid tapering possible.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/il-6-blockade-augments-the-anti-inflammatory-effect-without-increasing-the-side-effects-of-steroids-in-collagen-induced-arthritis/