Lianhuaqingwen capsule inhibits non-lethal doses of influenza virus-induced secondary Staphylococcus aureus infection in mice

Abstract

Ethnopharmacological relevanceLianhuaqingwen capsule (LH-C) is a traditional Chinese medicine (TCM), consisting of two prescriptions, Ma-xing-shi-gan-tang (MXSGT) and Yinqiao San. It has been proven to have antiviral, antibacterial, and immunomodulatory effects in recent years. Clinically, it is commonly used in the treatment of respiratory tract infections. Aim of the studyIt was demonstrated in our previous studies that LH-C has an effect of antivirus and inhibits influenza virus-induced bacterial adhesion to respiratory epithelial cells through down-regulation of cell adhesion molecules in vitro. However, LH-C's effect against influenza-induced secondary bacterial infection in animal studies remains unclear. Therefore, in the present study, we established a mouse model of infection with non-lethal doses of influenza virus(H1N1) and secondary infection of Staphylococcus aureus (S. aureus), to investigate the potential effects of LH-C. MethodsExperiments were carried out on BALB/c mice infecting non-lethal doses of H1N1 and non-lethal doses of S. aureus, and the viral, and bacterial doses were determined by observing and recording changes in the body weight, mortality, and pathological changes. Moreover, after LH-C treatment, the survival rate, body weight, lung index, viral titers, bacterial colonies, pathological changes, and the inflammatory cytokines in the mouse model have all been systematically determined. ResultsIn the superinfection models of H1N1 and S. aureus, the mortality rate was 100% in groups of mice infected with 20 PFU/50 μL of H1N1 and 105 CFU/mL of S. aureus, 20 PFU/50 μL of H1N1 and 106 CFU/mL of S. aureus, 4 PFU/50 μL of H1N1 and 106 CFU/mL of S. aureus. The mortality rate was 50% in the group of mice infected with 4 PFU/50 μL of H1N1 and 105 CFU/mL of S. aureus. The mortality rate was 37.5% in the group of mice infected with 20 PFU/50 μL of H1N1 alone and in the group of mice infected with 2 PFU/50 μL of H1N1 and 106 CFU/mL of S. aureus. The mortality rate in the group of mice infected with 2 PFU/50 μL of H1N1 and 106 CFU/mL of S. aureus was 30%. The infected mice of 2 PFU/50 μL of H1N1 and 106 CFU/mL of S. aureus had a weight loss of nearly 10%. About the histopathological changes in the lung tissue of infection mice, severe lung lesions were found in the superinfection models. LH-C improved survival in the superinfected mice, significantly reduced lung index, lowered viral titers and bacterial loads, and alleviated lung damage. It reduced lung inflammation by down-regulating mRNA expression levels of inflammatory mediators like IL-6, IL-1β, IL-10, TNF-α, IFN-β, MCP-1, and RANTES. ConclusionsWe found that superinfection from non-lethal doses of S. aureus following non-lethal doses of H1N1 was equally fatal in mice, confirming the severity of secondary infections. The ability of LH-C to alleviate lung injury resulting from secondary S. aureus infection induced by H1N1 was confirmed. These findings provided a further assessment of LH-C, suggesting that LH-C may have good therapeutic efficacy in influenza secondary bacterial infection disease.