Calcium Channel Blocker Prevents T Helper Type 2 Cell–mediated Airway Inflammation

Gomès, Bruno; Cabral, Marilena Djata; Gallard, Alexandra; Savignac, Magali; Paulet, Pierre; Druet, Philippe; Mariamé, Bernard; Moreau, Marc; Leclerc, Catherine; Guéry, Jean‐Charles; Pelletier, Lucette

doi:10.1164/rccm.200607-1026oc

Cited by 27 publications

(17 citation statements)

References 29 publications

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“…Calcium channel blockade has been associated with immunomodulation, although mostly downregulating inflammatory processes. [24][25][26] It may be that dihydropyridine use is a marker of worse systemic disease and therefore perioperative risk, although we did not find an association with aspirin, beta-blockers or statins. It would be premature to recommend not using dihydropyridines in the perioperative period, but there is a need for further studies on the effects of concurrent medications on patients undergoing surgery.…”

Section: Methodscontrasting

confidence: 76%

ARDS following oesophagectomy: a comparison of two trials

et al. 2017

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IntroductionThe Beta Agonist Lung Injury Trial-Prevention (BALTI-P) translational substudy and Vitamin D to Prevent Acute Lung Injury Following Oesophagectomy (VINDALOO) trials recruited patients undergoing oesophagectomy, 4 years apart. The acute respiratory distress syndrome (ARDS) rates were lower in the VINDALOO trial. We sought to identify changes between these two trials and identify risk factors for ARDS in oesophagectomy.MethodsThere were data available from 61 patients in the BALTI-P substudy and 68 from VINDALOO. Databases were available for both trials; additional data were collected. Multivariate logistic regression was used to analyse risk factors for ARDS and postoperative complications in the cohorts combined.ResultsLogistic regression analysis showed active smoking was associated with an increase in ARDS (OR 3.91; 95% CI 1.33 to 11.5) and dihydropyridine use (OR 5.34;95% CI 1.56 to 18.3). Hospital length of stay was longer for those who took dihydropyridines (median 29 days (IQR 17–42) vs 13 days (IQR 10–18), P=0.0007) or were diabetic (median 25 days (IQR 14–39) vs 13 (IQR 10–19), P=0.023) but not for current smokers (median in never/ex-smokers 13 (IQR 10–23) vs current smokers 15 (IQR 11–20), P=0.73).ConclusionsSmoking cessation trials should be promoted. Dihydropyridine effects perioperatively require further clinical and mechanistic evaluation. Patients undergoing oesophagectomy are a useful model for studying perioperative ARDS.

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Section: Methodscontrasting

confidence: 76%

ARDS following oesophagectomy: a comparison of two trials

et al. 2017

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“…The best known are the imidazole antimycotics (e.g., econazole and SFK-96365), 2-amino-ethyldiphenyl borate, and the pyrazole derivative YM-58483 (BTP2) (17). The latter has been reported to potently inhibit both Ca 2ϩ influx through CRAC channels and NFAT-driven IL-2 production in activated T cells (21), and to prevent Ag-induced airway eosinophilia and late phase asthmatic responses via Th2 cytokine inhibition in animal models (51).…”

Section: Discussionmentioning

confidence: 99%

Targeting Gut T Cell Ca2+ Release-Activated Ca2+ Channels Inhibits T Cell Cytokine Production and T-Box Transcription Factor T-Bet in Inflammatory Bowel Disease

Sabatino

Rovedatti

Kaur

et al. 2009

The Journal of Immunology

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Prolonged Ca2+ entry through Ca2+ release-activated Ca2+ (CRAC) channels is crucial in activating the Ca2+-sensitive transcription factor NFAT, which is responsible for directing T cell proliferation and cytokine gene expression. To establish whether targeting CRAC might counteract intestinal inflammation, we evaluated the in vitro effect of a selective CRAC inhibitor on T cell cytokine production and T-bet expression by lamina propria mononuclear cells (LPMC) and biopsy specimens from inflammatory bowel disease (IBD) patients. The inhibitory activity of the CRAC blocker was investigated through patch-clamp experiments on rat basophilic leukemia cells and fluorometric imaging plate reader intracellular Ca2+ assays using thapsigargin-stimulated Jurkat T cells and its detailed selectivity profile defined using a range of in vitro radioligand binding and functional assays. Anti-CD3/CD28-stimulated LPMC and biopsy specimens from 51 patients with IBD were cultured with a range of CRAC inhibitor concentrations (0.01–10 μM). IFN-γ, IL-2, IL-8, and IL-17 were analyzed by ELISA. T-bet was determined by immunoblotting. We found that the CRAC blocker concentration-dependently inhibited CRAC current in rat basophilic leukemia cells and thapsigargin-induced Ca2+ influx in Jurkat T cells. A concentration-dependent reduction in T-bet expression and production of IFN-γ, IL-2, IL-17, but not IL-8, was observed in IBD LPMC and biopsy specimens treated with the CRAC inhibitor. In conclusion, we provide evidence that the suppression of CRAC channel function may dampen the increased T cell response in the inflamed gut, thus suggesting a promising role for CRAC inhibitor drugs in the therapeutic management of patients with IBD.

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“…Gomes et al. reported that nicardipine improves experimental asthma by impairing inflammation, and could potentially be beneficial in the treatment of asthma [32].…”

Section: Discussionmentioning

confidence: 99%

Nicardipine vs. Saline Injection as Treatment for Peyronie’s Disease: A Prospective, Randomized, Single-Blind Trial

Soh

Kawauchi

Kanemitsu

et al. 2010

The Journal of Sexual Medicine

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Introduction Various conservative treatments for Peyronie’s disease (PD) have been attempted over the years. Intralesional verapamil injection has been tested in prospective randomized studies, but the effect of this treatment seems insufficient. Nicardipine is a calcium antagonist alternative to verapamil and is reportedly more effective in vitro. Aim The objective of our study was to evaluate the usefulness of intralesional nicardipine injection as a conservative treatment for PD in the transition period of acute and chronic phase. Methods Eighty-six patients (age: 38–72 years, mean: 52) were enrolled in this study. A total of 74 patients were assigned randomly to nicardipine group (10 mg diluted in 10 mL of distilled water daily, N=37) and control group (10 mL of saline water, N=37). A total of six injections were administrated biweekly. Mean Outcome Measure The subjects were assessed by International Index of Erectile Function (IIEF)-5 and international pain scale. The plaque size was measured by ultrasonography after 20 µg intracavernosal injection of alprostadil (prostaglandin E1). The penile curvature was also measured by taking a photograph at maximum rigidity. Results A reduction of pain score was seen throughout the course of treatment in both groups with a significant difference between the nicardipine and control groups (multiple analysis of variance test, P = 0.019). A significant improvement of IIEF-5 score occurred only in the nicardipine group at 48 weeks after the initiation of treatment (P <0.01). The plaque size was significantly reduced at 48 weeks only in the nicardipine group (12 points, P = 0.0004 by paired t-test). The penile curvature was significantly improved in both groups (P <0.01) without significant difference between them (P = 0.14). There were no severe side effects, such as hypotension or other cardiovascular events. Conclusion Our findings indicate that intralesional nicardipine injection is clinically effective as a conservative treatment for PD in the transition period of acute and chronic phase.

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Calcium Channel Blocker Prevents T Helper Type 2 Cell–mediated Airway Inflammation

Abstract: Nicardipine improves experimental asthma by impairing Th2-dependent inflammation. This study could provide a rationale for developing drugs selectively targeting DHP receptors of Th2 lymphocytes, potentially beneficial in the treatment of asthma.

Cited by 27 publications

References 29 publications

ARDS following oesophagectomy: a comparison of two trials

ARDS following oesophagectomy: a comparison of two trials

Targeting Gut T Cell Ca2+ Release-Activated Ca2+ Channels Inhibits T Cell Cytokine Production and T-Box Transcription Factor T-Bet in Inflammatory Bowel Disease

Nicardipine vs. Saline Injection as Treatment for Peyronie’s Disease: A Prospective, Randomized, Single-Blind Trial

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