PMID- 31640701
OWN - NLM
STAT- MEDLINE
DCOM- 20200330
LR  - 20201209
IS  - 1465-993X (Electronic)
IS  - 1465-9921 (Print)
IS  - 1465-9921 (Linking)
VI  - 20
IP  - 1
DP  - 2019 Oct 22
TI  - Rupintrivir reduces RV-induced T(H)-2 cytokine IL-4 in precision-cut lung slices 
      (PCLS) of HDM-sensitized mice ex vivo.
PG  - 228
LID - 10.1186/s12931-019-1175-y [doi]
LID - 228
AB  - 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 T(H)-2/T(H)-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-alpha, IFN-beta, IFN-gamma, TNF-alpha, 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 
      T(H)-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.
FAU - Danov, Olga
AU  - Danov O
AUID- ORCID: 0000-0001-6860-5610
AD  - 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.
FAU - Lasswitz, Lisa
AU  - Lasswitz L
AD  - 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.
FAU - Obernolte, Helena
AU  - Obernolte H
AD  - 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.
FAU - Hesse, Christina
AU  - Hesse C
AD  - 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.
FAU - Braun, Armin
AU  - Braun A
AD  - 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.
AD  - Institute of Immunology, Hannover Medical School, Carl-Neuberg Strasse 1, 30625, 
      Hannover, Germany.
FAU - Wronski, Sabine
AU  - Wronski S
AD  - 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.
FAU - Sewald, Katherina
AU  - Sewald K
AD  - 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. katherina.sewald@item.fraunhofer.de.
LA  - eng
PT  - Journal Article
DEP - 20191022
PL  - England
TA  - Respir Res
JT  - Respiratory research
JID - 101090633
RN  - 0 (Antiviral Agents)
RN  - 0 (Cytokines)
RN  - 0 (Isoxazoles)
RN  - 0 (Pyrrolidinones)
RN  - 207137-56-2 (Interleukin-4)
RN  - 47E5O17Y3R (Phenylalanine)
RN  - HG18B9YRS7 (Valine)
RN  - RGE5K1Q5QW (rupintrivir)
SB  - IM
MH  - Animals
MH  - Antiviral Agents/pharmacology
MH  - Cytokines/antagonists & inhibitors/immunology
MH  - Female
MH  - Interleukin-4/antagonists & inhibitors/*immunology
MH  - Isoxazoles/*pharmacology
MH  - Lung/drug effects/*immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Organ Culture Techniques
MH  - Phenylalanine/analogs & derivatives
MH  - Pyroglyphidae/*immunology
MH  - Pyrrolidinones/*pharmacology
MH  - *Rhinovirus
MH  - Th2 Cells/drug effects/*immunology
MH  - Valine/analogs & derivatives
PMC - PMC6805592
OTO - NOTNLM
OT  - Asthma
OT  - Exacerbation
OT  - Infection
OT  - Lung sections
OT  - Rhinovirus
COIS- Fraunhofer ITEM is a public non-profit research organization doing contract 
      research for e.g. pharmaceutical and biotech industry. All authors declare no 
      financial and non-financial interests.
EDAT- 2019/10/24 06:00
MHDA- 2020/03/31 06:00
PMCR- 2019/10/22
CRDT- 2019/10/24 06:00
PHST- 2019/06/24 00:00 [received]
PHST- 2019/08/28 00:00 [accepted]
PHST- 2019/10/24 06:00 [entrez]
PHST- 2019/10/24 06:00 [pubmed]
PHST- 2020/03/31 06:00 [medline]
PHST- 2019/10/22 00:00 [pmc-release]
AID - 10.1186/s12931-019-1175-y [pii]
AID - 1175 [pii]
AID - 10.1186/s12931-019-1175-y [doi]
PST - epublish
SO  - Respir Res. 2019 Oct 22;20(1):228. doi: 10.1186/s12931-019-1175-y.