tretinoin and Synovitis

All-trans retinoic acid has revolutionized the treatment of acute promyelocytic leukemia, but this therapy is often complicated by the all-trans retinoic acid syndrome. Here we report a patient with newly diagnosed acute promyelocytic leukemia who developed acute focal myositis, synovitis, and possible vasculitis, after receiving all-trans retinoic acid therapy. We review the existing literature on this rare clinical entity, all-trans retinoic acid-induced myositis. This condition can manifest as fever, myalgia, arthralgia, and Sweet syndrome, accompanied by distinct magnetic resonance findings involving the lower extremity musculature. Treatment consists of discontinuation of the offending drug and often high dose corticosteroids.

Topics: Adrenal Cortex Hormones; Antineoplastic Agents; Female; Humans; Leukemia, Promyelocytic, Acute; Middle Aged; Mononeuropathies; Myositis; Synovitis; Treatment Outcome; Tretinoin; Withholding Treatment

Current studies focused on the effects of all-trans-retinoic acid (ATRA) on synovial explants from rats with rheumatoid arthritis (RA) induced by lipopolysaccharides (LPS). In our study, synovial membranes were extracted aseptically from the quadriceps femoris of the knee joint of rats, and then incubated in medium containing 10% neonate bovine serum for 24 h adaptive culture. We first measured variations of correlation factors in synovium at 24, 48, 72, 96 and 120 h in control medium or in medium containing 20 ng/mL tumor necrosis factor alpha (TNF-α) (TNF-α-experiment). Then, we investigated the synovium exposed to three ATRA concentrations after 48 h incubation (ATRA-experiment). The effects of ATRA on synovitis were evaluated by observing the expression of inflammatory cytokines, angiogenic factors and the production of proteases in nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway and apoptosis and autophagy. In TNF-α-experiment, the secretion of nitric oxide (NO), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and matrix metalloproteinase-9 (MMP-9) increased significantly after TNF-α stimulation without pathological damage to the synovium. Hence, we successfully obtained the synovial explants model, which had longer inflammatory response time. In the ATRA-experiment, ATRA suppressed the secretion of IL-6 and NO, downregulated the NF-κB P65 and Bcl-2, increased levels of autophagy marker protein LC3, but different doses of ATRA showed inconsistent regulatory effects on VEGF and MMP-9. In short, ATRA inhibited TNF-α induced synovitis by the regulation of inflammatory cytokines and inhibiting NF-κB signal transduction and potentially promoting autophagy, apoptosis and angiogenesis, displaying its role in alleviating synovial inflammation in patients with RA.

Topics: Angiogenesis Inducing Agents; Animals; Apoptosis; Autophagy; Cytokines; Female; Interleukin-6; Male; Matrix Metalloproteinase 9; NF-kappa B; Nitric Oxide; Rats; Rats, Wistar; Signal Transduction; Synovial Membrane; Synovitis; Tretinoin; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

The present study was conducted to assess the effect of all-trans retinoic acid (ATRA) on synovial explants from rats with rheumatoid arthritis (RA) induced by lipopolysaccharides (LPS). In our study, synovial membranes were excised from the knees of healthy adult Wistar female rats under sterile conditions. We first investigated the synoviums incubated in a control medium or in a medium containing 10 μg/mL LPS, each for 24, 48, and 72 h (LPS-experiment). The changes in inflammatory response from the synoviums were observed at different culture times. Then, we assessed the synoviums exposed to different ATRA concentrations for 24 h (ATRA-experiment). The controls (blank, model group, and solvent groups) were set up. The effects of ATRA on synovitis were evaluated by measuring the production of cytokines, and nitric oxide (NO) and the expression of cartilage damage related proteases. In the LPS-experiment, LPS contributed to the release of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and matrix metalloproteinase-9 (MMP-9) in synovial explants. Importantly, LPS did not cause a significant pathological damage. The inflammatory response observed in this model was significant for 24 h, suggesting that LPS-induced synovial explants were successfully established. In the ATRA-experiment, ATRA suppressed the expression of IL-6, TNF-α, NO, a disintegrin and metalloprotease with thrombospondin motifs-4 (ADAMTS-4), MMP-3, and MMP-9. Taken together, ATRA exhibited inhibitory effects on LPS-induced synovial immune inflammatory response stimulated by the regulation of inflammatory mediators and cartilage damage related proteases in synovial explants, demonstrating a potential protective effect on synovitis and joint destruction in the patients with RA.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Cytokines; Disease Models, Animal; Female; Knee Joint; Lipopolysaccharides; Nitric Oxide; Rats; Rats, Wistar; Synovial Membrane; Synovitis; Tretinoin