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Simvastatin Suppresses Airway IL-17 and Upregulates IL-10 in Patients With Stable COPD.

Maneechotesuwan K, Wongkajornsilp A, Adcock IM, Barnes PJ - Chest (2015)

Bottom Line: At 4 weeks, there was a significant reduction in sputum IL-17A, IL-22, IL-6, and CXCL8 concentrations (mean difference, -16.4 pg/mL, P = .01; -48.6 pg/mL, P < .001; -45.3 pg/mL, P = .002; and -190.9 pg/mL, P = .007, respectively), whereas IL-10 concentrations, IDO messenger RNA expression (fold change), and IDO activity (kynurenine to tryptophan ratio) were markedly increased during simvastatin treatment compared with placebo treatment periods (mean difference, 24.7 pg/mL, P < .001; 1.02, P < .001; and 0.47, P < .001, respectively).The absolute sputum macrophage count, proportion of macrophages, and CAT score were reduced after simvastatin compared with placebo (mean difference, -0.16 × 106, P = .004; -14.1%, P < .001; and -3.2, P = .02, respectively).Values for other clinical outcomes were similar between the simvastatin and placebo treatments.

View Article: PubMed Central - PubMed

ABSTRACT

Background: Statins have immunomodulatory properties that may provide beneficial effects in the treatment of COPD. We investigated whether a statin improves the IL-17/IL-10 imbalance in patients with COPD, as has previously been demonstrated in patients with asthma.

Methods: Thirty patients with stable COPD were recruited to a double-blind, randomized, controlled, crossover trial comparing the effect of simvastatin, 20 mg po daily, with that of a matched placebo on sputum inflammatory markers and airway inflammation. Each treatment was administered for 4 weeks separated by a 4-week washout period. The primary outcome was the presence of T-helper 17 cytokines and indoleamine 2,3-dioxygenase (IDO) in induced sputum. Secondary outcomes included sputum inflammatory cells, FEV1, and symptoms using the COPD Assessment Test (CAT).

Results: At 4 weeks, there was a significant reduction in sputum IL-17A, IL-22, IL-6, and CXCL8 concentrations (mean difference, -16.4 pg/mL, P = .01; -48.6 pg/mL, P < .001; -45.3 pg/mL, P = .002; and -190.9 pg/mL, P = .007, respectively), whereas IL-10 concentrations, IDO messenger RNA expression (fold change), and IDO activity (kynurenine to tryptophan ratio) were markedly increased during simvastatin treatment compared with placebo treatment periods (mean difference, 24.7 pg/mL, P < .001; 1.02, P < .001; and 0.47, P < .001, respectively). The absolute sputum macrophage count, proportion of macrophages, and CAT score were reduced after simvastatin compared with placebo (mean difference, -0.16 × 106, P = .004; -14.1%, P < .001; and -3.2, P = .02, respectively). Values for other clinical outcomes were similar between the simvastatin and placebo treatments.

Conclusions: Simvastatin reversed the IL-17A/IL-10 imbalance in the airways and reduced sputum macrophage but not neutrophil counts in patients with COPD.

Trial registry: ClinicalTrials.gov; No.: NCT01944176; www.clinicaltrials.gov.

No MeSH data available.


Related in: MedlinePlus

A, Absolute macrophage counts were lower in response to simvastatin treatment to a greater extent than placebo. B, A similar pattern was seen in the proportion of macrophages (% of total cells). The data are expressed as mean (SD).
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fig05: A, Absolute macrophage counts were lower in response to simvastatin treatment to a greater extent than placebo. B, A similar pattern was seen in the proportion of macrophages (% of total cells). The data are expressed as mean (SD).

Mentions: The total cell counts recovered from sputum were similar after simvastatin and after placebo treatment (Table 3). After 4 weeks, the mean absolute and relative sputum macrophage counts were significantly reduced after simvastatin compared with placebo (mean absolute difference, −0.16 × 106 [95% CI, −0.26 to − 0.06], P = .004; −14.1% [95% CI, −21.0 to −7.1], P < .001) (Figs 5A, 5B, Table 3). There was a reciprocal increase in the relative proportion of sputum airway epithelial cells (mean proportion difference, 7.6%; 95% CI, 2.3-12.9; P = .007) (Table 3), but there was no significant changes in the absolute count of these cells or the counts and proportions of the other sputum cell phenotypes under simvastatin treatment.


Simvastatin Suppresses Airway IL-17 and Upregulates IL-10 in Patients With Stable COPD.

Maneechotesuwan K, Wongkajornsilp A, Adcock IM, Barnes PJ - Chest (2015)

A, Absolute macrophage counts were lower in response to simvastatin treatment to a greater extent than placebo. B, A similar pattern was seen in the proportion of macrophages (% of total cells). The data are expressed as mean (SD).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4631035&req=5

fig05: A, Absolute macrophage counts were lower in response to simvastatin treatment to a greater extent than placebo. B, A similar pattern was seen in the proportion of macrophages (% of total cells). The data are expressed as mean (SD).
Mentions: The total cell counts recovered from sputum were similar after simvastatin and after placebo treatment (Table 3). After 4 weeks, the mean absolute and relative sputum macrophage counts were significantly reduced after simvastatin compared with placebo (mean absolute difference, −0.16 × 106 [95% CI, −0.26 to − 0.06], P = .004; −14.1% [95% CI, −21.0 to −7.1], P < .001) (Figs 5A, 5B, Table 3). There was a reciprocal increase in the relative proportion of sputum airway epithelial cells (mean proportion difference, 7.6%; 95% CI, 2.3-12.9; P = .007) (Table 3), but there was no significant changes in the absolute count of these cells or the counts and proportions of the other sputum cell phenotypes under simvastatin treatment.

Bottom Line: At 4 weeks, there was a significant reduction in sputum IL-17A, IL-22, IL-6, and CXCL8 concentrations (mean difference, -16.4 pg/mL, P = .01; -48.6 pg/mL, P < .001; -45.3 pg/mL, P = .002; and -190.9 pg/mL, P = .007, respectively), whereas IL-10 concentrations, IDO messenger RNA expression (fold change), and IDO activity (kynurenine to tryptophan ratio) were markedly increased during simvastatin treatment compared with placebo treatment periods (mean difference, 24.7 pg/mL, P < .001; 1.02, P < .001; and 0.47, P < .001, respectively).The absolute sputum macrophage count, proportion of macrophages, and CAT score were reduced after simvastatin compared with placebo (mean difference, -0.16 × 106, P = .004; -14.1%, P < .001; and -3.2, P = .02, respectively).Values for other clinical outcomes were similar between the simvastatin and placebo treatments.

View Article: PubMed Central - PubMed

ABSTRACT

Background: Statins have immunomodulatory properties that may provide beneficial effects in the treatment of COPD. We investigated whether a statin improves the IL-17/IL-10 imbalance in patients with COPD, as has previously been demonstrated in patients with asthma.

Methods: Thirty patients with stable COPD were recruited to a double-blind, randomized, controlled, crossover trial comparing the effect of simvastatin, 20 mg po daily, with that of a matched placebo on sputum inflammatory markers and airway inflammation. Each treatment was administered for 4 weeks separated by a 4-week washout period. The primary outcome was the presence of T-helper 17 cytokines and indoleamine 2,3-dioxygenase (IDO) in induced sputum. Secondary outcomes included sputum inflammatory cells, FEV1, and symptoms using the COPD Assessment Test (CAT).

Results: At 4 weeks, there was a significant reduction in sputum IL-17A, IL-22, IL-6, and CXCL8 concentrations (mean difference, -16.4 pg/mL, P = .01; -48.6 pg/mL, P < .001; -45.3 pg/mL, P = .002; and -190.9 pg/mL, P = .007, respectively), whereas IL-10 concentrations, IDO messenger RNA expression (fold change), and IDO activity (kynurenine to tryptophan ratio) were markedly increased during simvastatin treatment compared with placebo treatment periods (mean difference, 24.7 pg/mL, P < .001; 1.02, P < .001; and 0.47, P < .001, respectively). The absolute sputum macrophage count, proportion of macrophages, and CAT score were reduced after simvastatin compared with placebo (mean difference, -0.16 × 106, P = .004; -14.1%, P < .001; and -3.2, P = .02, respectively). Values for other clinical outcomes were similar between the simvastatin and placebo treatments.

Conclusions: Simvastatin reversed the IL-17A/IL-10 imbalance in the airways and reduced sputum macrophage but not neutrophil counts in patients with COPD.

Trial registry: ClinicalTrials.gov; No.: NCT01944176; www.clinicaltrials.gov.

No MeSH data available.


Related in: MedlinePlus