Shikonin alleviates collagen-induced arthritis mice by inhibiting M1 macrophage polarization.

OBJECTIVE: To investigate the effects of shikonin (SKN) on M1 and M2 polarization of macrophages both and . METHODS: Collagen-induced arthritis (CIA) in male DBA/1 mice were treated with a dose of 4 mg/kg/day of SKN for 23 d ( = 6/group). The histopathology of inflamed joints in CIA mice was evaluated to test the anti-arthritic effect of SKN. M1/M2 polarization of macrophages induced by lipopolysaccharide (LPS) and interferon (IFN)-γ or interleukin (IL)-4 and IL-13, were used to assess the effect of SKN (0.05, 0.1, and 0.2 µM). The effect of SKN on the protein expression of nitric oxide synthase, arginase, CD68, and CD206 was evaluated using western blot analysis. RESULTS: The results of this study revealed that SKN delayed the arthritis feet symptom score, reduced the incidence rate of arthritis, and relieved the inflammation of joints in CIA mice. SKN inhibited M1 macrophage polarization but did not affect M2 macrophage polarization in the joints of CIA mice. Moreover, SKN inhibited M1 polarization induced by LPS and IFN-γ, but did not affect M2 polarization induced by IL-4 and IL-13. CONCLUSION: These findings suggest that SKN alleviated CIA through inhibiting M1 macrophage polarization and has great potential as a new drug for RA treatment.

Meta-analysis of Risk Factors for Rheumatoid Arthritis associated Interstitial Lung Disease / 中华风湿病学杂志

Objective:To evaluate the risk factors of rheumatoid arthritis associated interstitial lung disease (RA-ILD).Methods:Databases including PubMed, Sinomed, Embase, Wiley Online library were searched to collect studies on risk factors of RA-ILD. The deadline of the search was January 1 2021. Newcastle-Ottawa Scale (NOS) was used to assess the literature quality, data was extracted and analyzed by Statistical software in eligible studies.Results:This meta-analysis included 36 studies involving 3 280 patients with RA-ILD and 25 510 RA controls patients. The Incidence of RA-ILD was 6.25%. The risk of RA-ILD was 2.51 times greater in men than in women [ OR(95% CI)=2.51(2.25, 2.80)]. The mean onset age of patients with RA-ILD was 7.47 years [56.50 vs 49.04, 95% CI(6.56, 8.38)] older than those of patients with RA-nILD. The mean duration of patients with RA-ILD was 1.11 years longer than that of patients with RA-nILD [7.73 vs 6.62, 95% CI(0.68, 1.55)]. The risk of RA-ILD was two times greater in smoker than in non-smoker [ OR(95% CI)=2.25(2.01, 2.52]). Moderate evidence indicated that higher erythrocyte sedimentation rate(ESR), C-reactive protein(CRP), disease activity score in 28 joints (DAS28)-ESR were risk factors for RA-ILD[Stan-dard Mean Difference ( SMD)(95% CI)=0.25(0.18, 0.31); SMD(95% CI)=0.25(0.18, 0.32); SMD(95% CI)=0.36(0.27, 0.45), respectively). The pooled [ OR(95% CI)=1.71(1.45, 2.01)] in rheumatoid factor (RF) positive and [ OR(95% CI)=2.41(1.80, 3.23)] anti-CCP antibody positive for the risk of RA-ILD. Conclusion:Male, smoking, older age of disease onset, long disease duration, elevated erythrocyte sedimentation rate, high C-reactive protein level, high DAS28-ESR, positive RF and anti-cyclic peptide containing citrulline antibody were risk factors for RA-ILD.