Abstract

BackgroundRespiratory 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.MethodsNaïve 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.ResultsEGY-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.ConclusionThe 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.

Highlights

  • The common cold is one of the leading causes for consultation of a physician

  • Viral load in bronchoalveolar lavage fluid (BALF) and lung homogenate was determined by tissue culture infective dose 50 (TCID50) assay as well as immunofluorescence staining of BALF cells using anti-respiratory syncytial virus (RSV) antibody and microscopic analysis

  • In the mild model of virus induced common cold used for the study, RSV infection, induced an inflammatory immune response characterized by early infiltration of predominantly neutrophilic granulocytes as indicated by the significant increase of BALF neutrophil numbers on day 1 p.i

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Summary

Introduction

The common cold is one of the leading causes for consultation of a physician. Despite its generally mild course of disease the common cold continues to be a massive burden in terms of quality of life and socioeconomic impact due to its high prevalence [1,2]. While rather innocuous as common cold pathogen in adults, RSV can cause severe and life-threatening conditions such as pneumonia and bronchiolitis in infants with a high mortality rate [4]. Both rhinovirus and RSV are commonly used in in vitro and in vivo respiratory infection models for preclinical research and further investigation of the complex inflammatory mechanisms of the host-pathogen-interaction. Respiratory viruses such as respiratory syncytial virus (RSV) or rhinovirus are one of the major causes for respiratory tract infections causing common cold disease. 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.

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