Engystol reduces onset of experimental respiratory syncytial virus-induced respiratory inflammation in mice by modulating macrophage phagocytic capacity

PLoS One. 2018 Apr 19;13(4):e0195822. doi: 10.1371/journal.pone.0195822. eCollection 2018.


Background: Respiratory viruses such as respiratory syncytial virus (RSV) or rhinovirus are one of the major causes for respiratory tract infections causing common cold disease. Respiratory viral infections range from mild symptoms in adults to serious illness especially in the very young or elderly as well as patients suffering from lung diseases or being immunocompromised due to other reasons. Engystol (EGY-2) is a multicomponent, multitarget preparation consisting of Vincetoxicum hirundinaria and Sulfur in various dilutions. The study objective was to test the effect of EGY-2 on the innate immune response during the early onset of respiratory viral infection in vivo as exemplified in a mouse model of RSV-induced respiratory inflammation.

Methods: Naïve BALB/c mice were infected with 1x106 infectious units RSV A2 intranasally to cause a mild respiratory infection. EGY-2 was administered daily per oral gavage starting seven days prior to RSV infection at doses of 0.4 to 5.1 tablets/kg. Control groups received placebo treatment. Animals were sacrificed 1 to 3 days post infection (p.i.) to analyse the infection and induced immune response in the lung. Viral load in bronchoalveolar lavage fluid (BALF) and lung homogenate was determined by TCID50 assay as well as immunofluorescence staining of BALF cells using anti-RSV antibody and microscopic analysis. The RSV induced immune response was assessed by evaluation of BALF differential cell count, BALF cytokine secretion and analysis of the phagocytic capacity of alveolar macrophages.

Results: EGY-2 significantly reduced the RSV induced neutrophil and early lymphocyte influx on day 1 p.i. in BALF. EGY-2 treatment significantly diminished the RSV induced secretion of pro-inflammatory cytokines such as IFN-γ, IL-1β, IL-6, KC and TNF-α at day 1. EGY-2 treatment was not protective for RSV infection per se, as no alteration in the viral load in lung and BALF was detected. Enhanced numbers of phagocytic-active macrophages were observed in EGY-2 treated animals on day 1 and this macrophage population showed strongly enhanced phagocytic activity on day 1 and day 3.

Conclusion: The data suggest a beneficial immunomodulatory effect of EGY-2 during early onset of respiratory viral infection in vivo, mediated by stimulation of macrophage phagocytosis, resulting in a reduced innate inflammatory response in terms of neutrophil and early lymphocyte infiltration as well as reduced inflammatory cytokine secretion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / immunology
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Macrophage Activation / drug effects
  • Macrophage Activation / immunology
  • Macrophages / drug effects*
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Macrophages, Alveolar / drug effects
  • Macrophages, Alveolar / immunology
  • Macrophages, Alveolar / metabolism
  • Macrophages, Alveolar / pathology
  • Mice
  • Neutrophil Infiltration / drug effects
  • Neutrophil Infiltration / immunology
  • Neutrophils / drug effects
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Neutrophils / pathology
  • Phagocytosis / drug effects*
  • Phagocytosis / immunology*
  • Plant Extracts / pharmacology*
  • Respiratory Syncytial Virus Infections / drug therapy
  • Respiratory Syncytial Virus Infections / immunology*
  • Respiratory Syncytial Virus Infections / metabolism
  • Respiratory Syncytial Virus Infections / virology*
  • Respiratory Syncytial Viruses / immunology*
  • Viral Load


  • Cytokines
  • Plant Extracts
  • engystol-N

Grants and funding

The study was funded by Biologische Heilmittel Heel GmbH, Baden-Baden, Germany, which employed authors JD, YB and BS at the time this work was generated and reviewed, and authorized the manuscript. The funder provided support in form of salaries for the authors JD, YB, and BS, and provided the test substance and placebo, but was not actively involved in practical implementation data collection, analysis and decision to publish. The specific roles of these authors are articulated in the ‘authors contributions’ section.