Abstract
Objective Influenza virus poses a major threat to human health and has serious morbidity and mortality which commonly occurs in high-risk populations. Pharynx and larynx of the upper respiratory tract mucosa is the first defense line against influenza virus infection. However, the ability of the pharynx and larynx organ to eliminate the influenza pathogen is still not clear under different host conditions. Methods In this study, a mouse model of kidney yang deficiency syndrome (KYDS) was used to mimic high-risk peoples. Two different methods of influenza A (H1N1) virus infection by nasal dropping or tracheal intubation were applied to these mice, which were divided into four groups: normal intubation (NI) group, normal nasal dropping (ND) group, model intubation (MI) group, and model nasal dropping (MD) group. The normal control (NC) group was used as a negative control. Body weight, rectal temperature, and survival rate were observed every day. Histopathologic changes, visceral index, gene expressions of H1N1, cytokine expressions, secretory IgA (SIgA) antibodies of tracheal lavage fluids in the upper respiratory tract, and bronchoalveolar lavage fluids were analyzed by ELISA. Results The MD group had an earlier serious morbidity and mortality than the others. MI and NI groups became severe only in the 6th to 7th day after infection. The index of the lung increased significantly in NI, MI, and MD groups. Conversely, indices of the thymus and spleen increased significantly in NC and ND groups. H&E staining showed severe tissue lesions in MD, MI, and NI groups. H1N1 gene expressions were higher in the MD group compared with the MI group on the 3rd day; however, the MD group decreased significantly on the 7th day. IL-6 levels increased remarkably, and SIgA expressions decreased significantly in the MD group compared with the NC group. Conclusions SIgA secretions are influenced directly by different conditions of the host in the pharynx and larynx in the upper respiratory tract mucosa. In the KYDS virus disease mode, SIgA expressions could be inhibited severely, which leads to serious morbidity and mortality after influenza A virus infection. The SIgA expressions of the pharynx and larynx would be an important target in high-risk populations against the influenza A virus for vaccine or antiviral drugs research.
Highlights
Influenza is a highly infectious disease that causes a worldwide public health problem in millions of peoples per year. e most common influenza A (H1N1) virus can cause seasonal infections with significant morbidity and mortality in elderly and high-risk adults all around the world [1,2,3,4,5]
In order to mimic the high-risk population, we established a kidney yang deficiency syndrome (KYDS) mice model by injecting estradiol benzoate for seven days as previously described; the body weight of the KYDS group was significantly lower than normal control mice from the 3rd day to the 7th day (P < 0.01) (Figure 1(a)). e rectal temperature of the KYDS group decreased significantly compared with the normal group for six days (P < 0.05) (Figure 1(b)). e spontaneous activity and swimming time of KYDS mice were obviously lower than the control group (P < 0.05; P < 0.01) (Figures 1(c) and 1(d)). ese results showed that the KYDS mice model was established successfully [21, 22]
normal intubation (NI), model nasal dropping (MD), and model intubation (MI) groups decreased significantly in weight and temperature compared with the normal control (NC) and nasal dropping (ND) groups (P < 0.01, Figures 2(a) and 2(b)). e rectal temperature of the MD group reduced significantly from the 2nd to the 3rd day (P < 0.01, Figure 2(b))
Summary
Influenza is a highly infectious disease that causes a worldwide public health problem in millions of peoples per year. e most common influenza A (H1N1) virus can cause seasonal infections with significant morbidity and mortality in elderly and high-risk adults all around the world [1,2,3,4,5]. When an epidemiological investigation was conducted in 2137 healthy elderly above 60-year-old residents, the results showed that the incidence rate of kidney deficiency was 78.80% [16], and the kidney deficiency syndrome prevalence in participants showed an increasing trend with increasing age and deteriorating health status [17]. Another epidemiological study on 2,067 adults aged >60 years revealed that 45.33% suffered from KYDS, showing that KYDS is the predominant TCM syndrome in high-risk populations [18] and these elderly groups are at increased risk for serious flu complications. Another epidemiological study on 2,067 adults aged >60 years revealed that 45.33% suffered from KYDS, showing that KYDS is the predominant TCM syndrome in high-risk populations [18] and these elderly groups are at increased risk for serious flu complications. erefore, a key challenge is how to reduce the high mortality in susceptible population infected with the influenza virus
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