Source: International Congress 2014 – New treatments for cough, asthma, COPD and ILDs
Disease area: Airway diseases

Abstract

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 b-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 (IFNg 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, IFNg 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 IFNg 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 IFNg 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.

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Citations should be made in the following way:
J. Knobloch, Y. Yakin, B. Grensemann, S. Körber, D. Jungck, A. Koch (Bochum, Cologne, Germany). Simvastatin suppresses the activity of Th2 and Tc2 cells in atopic asthma and in COPD. Eur Respir J 2014; 44: Suppl. 58, 1517

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