RESUMEN
Rhinovirus (RV) is the predominant virus causing respiratory tract infections. Bronchobini® is a low dose multi component, multi target preparation used to treat inflammatory respiratory diseases such as the common cold, described to ease severity of symptoms such as cough and viscous mucus production. The aim of the study was to assess the efficacy of Bronchobini® in RV infection and to elucidate its mode of action. Therefore, Bronchobini®'s ingredients (BRO) were assessed in an ex vivo model of RV infection using mouse precision-cut lung slices, an organotypic tissue capable to reflect the host immune response to RV infection. Cytokine profiles were assessed using enzyme-linked immunosorbent assay (ELISA) and mesoscale discovery (MSD). Gene expression analysis was performed using Affymetrix microarrays and ingenuity pathway analysis. BRO treatment resulted in the significant suppression of RV-induced antiviral and pro-inflammatory cytokine release. Transcriptome analysis revealed a multifactorial mode of action of BRO, with a strong inhibition of the RV-induced pro-inflammatory and antiviral host response mediated by nuclear factor kappa B (NFkB) and interferon signaling pathways. Interestingly, this was due to priming of these pathways in the absence of virus. Overall, BRO exerted its beneficial anti-inflammatory effect by priming the antiviral host response resulting in a reduced inflammatory response to RV infection, thereby balancing an otherwise excessive inflammatory response.
Asunto(s)
Antivirales/farmacología , Inductores de Interferón/farmacología , Interferones/metabolismo , Pulmón/efectos de los fármacos , Infecciones por Picornaviridae/tratamiento farmacológico , Extractos Vegetales/farmacología , Transcriptoma , Animales , Antivirales/uso terapéutico , Femenino , Inductores de Interferón/uso terapéutico , Pulmón/metabolismo , Pulmón/virología , Ratones , Ratones Endogámicos BALB C , Infecciones por Picornaviridae/inmunología , Infecciones por Picornaviridae/virología , Extractos Vegetales/uso terapéutico , Rhinovirus/efectos de los fármacos , Rhinovirus/patogenicidad , Transducción de SeñalRESUMEN
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-1ß, 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.