RT Journal Article
SR Electronic
T1 Simvastatin suppresses the activity of Th2 and Tc2 cells in atopic asthma and in COPD
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P1517
VO 44
IS Suppl 58
A1 Jürgen Knobloch
A1 Yakup Yakin
A1 Barbara Grensemann
A1 Sandra Körber
A1 David Jungck
A1 Andrea Koch
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/P1517.abstract
AB Rationale: Retrospective studies suggest simvastatin (SA) as an alternative anti-inflammatory therapy for asthma and COPD. It is unknown, which cell types are influenced by SA. SA might require activation to β-hydroxy-SA (BHSA) by carboxylesterases, which are primarily expressed in monocytes (compared to T cells).Hypothesis: SA reduces the release of Th1/Tc1 and Th2/Tc2 key cytokines (IFNγ or IL-5 respectively).Methods: Pure circulating CD4+ and CD8+ T cells and T cell populations in peripheral blood mononuclear cells (PBMCs, which include monocytes) were activated ex vivo towards Th1/Tc1 or Th2/Tc2 and incubated with SA and BHSA (1-1000nM). Cytokines were measured by ELISA comparative between never-smokers (NS), smokers without (S) and with COPD and never-smokers with mild/moderate atopic asthma (A); n=9/7/14/10.Results: In the presence and absence of monocytes, IFNγ was induced by activation of CD4+ or CD8+ cells towards Th1 or Tc1, respectively. Activation towards Th2 and Tc2 induced IL-5, which was increased in COPD vs. NS (p<0.05). BHSA but not SA reduced IL-5 in pure Th2 and Tc2 cells but not IFNγ in pure Th1 and Tc1 cells - regardless of whether BHSA was added prior to or 24 h after T cell activation (each p<0.05). In the presence of monocytes (in PBMCs) SA reduced IL-5 from Th2/Tc2 cells without differences between cohorts and increased IFNγ from Th1/Tc1 cells in S and COPD (each p<0.05) but not in NS and A.Discussion: SA requires activation in monocytes to modulate T cell cytokine expression. SA suppresses Th2/Tc2-associated cytokine production in asthma and COPD but might enhance Th1 inflammation in COPD. SA could have anti-inflammatory effects in asthma.