Telmisartan is an angiotensin-II receptor blocker and acts as a selective modulator of peroxisome proliferator-activated receptor gamma (PPARγ). Several studies have demonstrated that telmisartan ameliorates depression and memory dysfunction and reduces brain inflammation. We hypothesized that the beneficial effects of telmisartan on brain could be due to modulation of the blood-brain barrier (BBB) function. Here, we examined the effect of telmisartan on tumor necrosis factor alpha (TNF-α)-induced expression of intercellular adhesion molecule 1 (ICAM-1) which plays an important role in leukocyte transcytosis through the BBB. Telmisartan blocked TNF-α-induced ICAM-1 expression and leukocyte adhesion in U87MG human glioma cells but showed no effect on human brain microvascular endothelial cells. In U87MG cells, a PPAR antagonist, GW9662 did not block the effect of telmisartan on ICAM1 expression but rather potentiated. Moreover, GW9662 caused no change in TNF-α-induced ICAM-1 expression, suggesting no implication of PPARγ in the telmisartan effect. Further studies showed that telmisartan blocked TNF-α-induced activation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and nuclear factorkappa B (NF-κB). In contrast, inhibitors of JNK, ERK1/2 and NF-κB but not p38, blocked ICAM-1 expression induced by TNF-α.Thus, our findings suggest that the beneficial effect of telmisartan is likely due to the reduction of astrocytic ICAM1 expression and leukocytes adhesion to astrocytes, and that this response was mediated by the inhibition of JNK/ERK1/2/NF-κB activation and in the PPAR-independent manner. In conclusion, this study enhances our understanding of the mechanism by which telmisartan exerts the beneficial brain function.

BACKGROUND/AIMS: To determine the changes in body weight and bone mineral density in patients with ankylosing spondylitis (AS) receiving anti-tumor necrosis factor-alpha (TNF-alpha) treatment. METHODS: Thirty-one patients with AS (25 males and 6 females) who fulfilled the Modified New York Criteria for AS were included in this retrospective study. All patients had active disease that eventually required anti-TNF-alpha treatment. Each patient received anti-TNF-alpha treatment (etanercept 25 mg twice weekly or adalimumab 40 mg twice monthly) for more than 2 years. Body weight, disease activity as Bath ankylosing spondylitis disease activity index (BASDAI), C-reactive protein, erythrocyte sedimentation rate (ESR), lumbar bone mineral density (LBMD), and femoral bone mineral density (FBMD) were measured at baseline and at 1 and 2 years after initiating anti-TNF-alpha treatment. RESULTS: There was a significant increase in mean body weight at 1 year (1.1 +/- 3.8 kg) and at 2 years (1.7 +/- 4.8 kg) compared with baseline. The gains in mean BMD of the lumbar spine were significant at 1 year (0.4 +/- 0.4) and 2 years (0.5 +/- 0.7) compared with baseline. Mean BMD of the femur was also increased at 1 year (0.08 +/- 0.7) and 2 years (0.1 +/- 0.8) compared with baseline, but these differences were not statistically significant. There were significant decreases in BASDAI at 1 year (-3.3 +/- 2.8) and at 2 years (-3.6 +/- 2.8) compared with baseline. CONCLUSIONS: This study showed significant increases in body weight, lumbar BMD, and BASDAI at 1 year and 2 years in patients with ankylosing spondylitis after receiving anti-TNF-alpha treatment.
Antibodies, Monoclonal, Humanized ; Baths ; Blood Sedimentation ; Body Weight* ; Bone Density* ; C-Reactive Protein ; Cachexia ; Femur ; Humans ; Male ; Necrosis* ; Retrospective Studies ; Spine ; Spondylitis ; Spondylitis, Ankylosing* ; Adalimumab

BACKGROUND/AIMS: To determine the changes in body weight and bone mineral density in patients with ankylosing spondylitis (AS) receiving anti-tumor necrosis factor-alpha (TNF-alpha) treatment. METHODS: Thirty-one patients with AS (25 males and 6 females) who fulfilled the Modified New York Criteria for AS were included in this retrospective study. All patients had active disease that eventually required anti-TNF-alpha treatment. Each patient received anti-TNF-alpha treatment (etanercept 25 mg twice weekly or adalimumab 40 mg twice monthly) for more than 2 years. Body weight, disease activity as Bath ankylosing spondylitis disease activity index (BASDAI), C-reactive protein, erythrocyte sedimentation rate (ESR), lumbar bone mineral density (LBMD), and femoral bone mineral density (FBMD) were measured at baseline and at 1 and 2 years after initiating anti-TNF-alpha treatment. RESULTS: There was a significant increase in mean body weight at 1 year (1.1 +/- 3.8 kg) and at 2 years (1.7 +/- 4.8 kg) compared with baseline. The gains in mean BMD of the lumbar spine were significant at 1 year (0.4 +/- 0.4) and 2 years (0.5 +/- 0.7) compared with baseline. Mean BMD of the femur was also increased at 1 year (0.08 +/- 0.7) and 2 years (0.1 +/- 0.8) compared with baseline, but these differences were not statistically significant. There were significant decreases in BASDAI at 1 year (-3.3 +/- 2.8) and at 2 years (-3.6 +/- 2.8) compared with baseline. CONCLUSIONS: This study showed significant increases in body weight, lumbar BMD, and BASDAI at 1 year and 2 years in patients with ankylosing spondylitis after receiving anti-TNF-alpha treatment.
Antibodies, Monoclonal, Humanized ; Baths ; Blood Sedimentation ; Body Weight* ; Bone Density* ; C-Reactive Protein ; Cachexia ; Femur ; Humans ; Male ; Necrosis* ; Retrospective Studies ; Spine ; Spondylitis ; Spondylitis, Ankylosing* ; Adalimumab