ABSTRACT
BACKGROUND: Indirubin, a constituent of the Chinese herbal medicine "Qing-Dai," has anti-cancer and anti-inflammatory activities. We aimed to evaluate the efficacy of indirubin for ameliorating colonic inflammation in a mouse model of inflammatory bowel disease. METHODS: Mice with dextran sulfate sodium (DSS)-induced acute and chronic colitis were treated with indirubin in their diet. Clinical and histologic changes were evaluated. In addition, colon levels of interleukin-6, a critical pro-inflammatory mediator, was detected by enzyme-linked immunosorbent assay. RESULTS: In the model of acute colitis, indirubin treatment improved the loss of body weight. Histology of colonic tissue revealed that indirubin treatment improved the histology grading of colitis (P = 0.02), the extent of submucosal fibrosis (P = 0.018), the number of mucosal toluidine blue-positive cells (P = 0.004) and colon length (P = 0.01). In the model of chronic colitis, indirubin treatment had no significant effect on pathologic findings except for colon length (P = 0.003). However, indirubin administration significantly reduced colon levels of interleukin-6 in the chronic-colitis model (P = 0.001). CONCLUSION: Our study clearly showed that oral intake of indirubin can improve murine DSS-induced colitis (which mimics human inflammatory bowel disease).
ABSTRACT
Patients with rheumatoid arthritis (RA) have an increased cardiovascular (CV) risk. This study aimed to analyze the effects of Tofacitinib treatment, a Janus kinase inhibitor, on atherosclerosis in patients with RA. Patients with an active RA (28-joint disease activity score-erythrocyte sedimentation rate > 3.2) despite methotrexate (MTX) treatment 12 mg/week were included in this open-label prospective study and started on Tofacitinib (10 mg/day, 5 mg twice/day). Japanese guideline does not allow high dose of MTX. All patients used a stable dosage of MTX, steroids, and statins or lipid-lowering drugs. The primary endpoint was the comparison of the carotid intima-media thickness (CIMT) at the baseline and 54 weeks after Tofa treatment. Clinical data were collected at regular visits. Forty-six patients completed this study. CIMT did not significantly change from baseline to 54 weeks (1.09 ± 0.69 and 1.08 ± 0.78 mm, p = 0.82). In 12 patients who had atherosclerosis at baseline (carotid intima-media thickness > 1.10 mm), there was a significant decrease in CIMT (0.05± 0.026 mm; p < 0.05). However, the decrease in CIMT was of limited clinical significance. Tofacitinib increased fasting total cholesterol levels from baseline to 54 weeks (216 ± 25.3 and 234 ± 28.8 mg/dL, p < 0.01). Tofacitinib affects atherosclerosis in patients with active RA The CIMT in RA patients was stable. Tofacitinib decreased the CIMT of patients who had increased CIMT at baseline. Tofacitinib reduced RA disease activity and limited vascular damage despite up-regulating cholesterol in patients with an active RA.
Subject(s)
Arthritis, Rheumatoid/drug therapy , Atherosclerosis/prevention & control , Carotid Arteries/drug effects , Carotid Intima-Media Thickness , Cholesterol/blood , Piperidines/administration & dosage , Protein Kinase Inhibitors/administration & dosage , Pyrimidines/administration & dosage , Pyrroles/administration & dosage , Adult , Aged , Arthritis, Rheumatoid/complications , Atherosclerosis/diagnosis , Atherosclerosis/etiology , Carotid Arteries/diagnostic imaging , Cohort Studies , Drug Administration Schedule , Female , Humans , Intention to Treat Analysis , Male , Methotrexate/administration & dosage , Middle Aged , Risk Factors , Single-Blind Method , Surveys and Questionnaires , Ultrasonography , Up-RegulationABSTRACT
OBJECTIVE: The aim of this study was to analyse the effects of therapy with tocilizumab (TCZ), an anti-IL-6 receptor antibody, on BMD of the lumbar spine and femoral neck in patients with RA. METHODS: Eighty-six patients with active RA (indicated by a 28-joint DAS ESR >3.2) despite treatment with MTX 12 mg/week were included in this open-label prospective study and started on TCZ (8 mg/kg every 4 weeks). All patients used a stable dosage of MTX and were not allowed to use steroids or bisphosphonates during the study period. BMD of the lumbar spine and femoral neck was measured by dual-energy X-ray absorptiometry at baseline and 52 weeks after initiating TCZ. RESULTS: Seventy-eight patients completed this study. BMD of the lumbar spine and femoral neck remained stable after 1 year of TCZ treatment. In 33 patients who had osteopenia at baseline, there was a significant increase in BMD of the lumbar spine [mean 0.022 (s.d.) 0.042, P < 0.05] and femoral neck [0.024 (0.0245), P < 0.05]. CONCLUSION: TCZ affects BMD in patients who had active RA despite treatment with MTX. BMD of the lumbar spine and femoral neck in patients with normal BMD at baseline was stable. TCZ increased the BMD of patients who had osteopenia at baseline.
