Rupintrivir reduces RV-induced TH-2 cytokine IL-4 in precision-cut lung slices (PCLS) of HDM-sensitized mice ex vivo

  • Respir Res. 2019 Oct 22;20(1):228. doi: 10.1186/s12931-019-1175-y.
Olga Danov  1 ,  Lisa Lasswitz  1 ,  Helena Obernolte  1 ,  Christina Hesse  1 ,  Armin Braun  1  2 ,  Sabine Wronski  1 ,  Katherina Sewald  3
Affiliations
  • 1. Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Member of Fraunhofer International Consortium for Anti-Infective Research (iCAIR), Nikolai-Fuchs-Strasse 1, 30625, Hannover, Germany.
  • 2. Institute of Immunology, Hannover Medical School, Carl-Neuberg Strasse 1, 30625, Hannover, Germany.
  • 3. Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Member of Fraunhofer International Consortium for Anti-Infective Research (iCAIR), Nikolai-Fuchs-Strasse 1, 30625, Hannover, Germany. [email protected].
PMID: 31640701 DOI: 10.1186/s12931-019-1175-y
Abstract

Background: Antiviral drugs such as rupintrivir may have an immune-modulatory effect in experimentally induced allergic asthma with subsequent RV Infection. We infected lung slices of house-dust Mite (HDM)-sensitized asthmatic mice ex vivo with human rhinovirus (RV) and investigated the effect of the Antiviral drug rupintrivir on RV-induced cytokine response in lung tissue of HDM-sensitized mice ex vivo.

Methods: Mice were sensitized with HDM. Precision-cut lung slices (PCLS) were prepared from HDM-sensitized or non-sensitized mice. Lung slices were infected ex vivo with RV or RV together with rupintrivir. Modulation of immune responses was evaluated by cytokine secretion 48 h post Infection.

Results: In vivo HDM sensitization resulted in a TH-2/TH-17-dominated cytokine response that persisted in PCLS ex vivo. RV Infection of PCLS from non-sensitized mice resulted in the induction of an Antiviral and pro-inflammatory immune response, as indicated by the secretion of IFN-α, IFN-β, IFN-γ, TNF-α, MCP-1, IP-10, IL-10, and IL-17A. In contrast, PCLS from HDM-sensitized mice showed an attenuated Antiviral response, but exaggerated IL-4, IL-6, and IL-10 secretion upon Infection. Rupintrivir inhibited exaggerated pro-inflammatory cytokine IL-6 and TH-2 cytokine IL-4 in HDM-sensitized mice.

Conclusions: In summary, this study demonstrates that treatment with rupintrivir influences virus-induced IL-4 and IL-6 cytokine release under experimental conditions ex vivo.

Keywords
Asthma; Exacerbation; Infection; Lung sections; Rhinovirus.
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