Lianhua Qingke Tablet in severe pneumonia: Clinical efficacy and immunoregulatory mechanisms

Lianhua Qingke (LHQK), a traditional Chinese medicine, has shown efficacy in treating acute and chronic bronchitis and bronchiolitis. However, the specific mechanism underlying the therapeutic effects of LHQK on severe pneumonia is not clear.

Severe pneumonia remains a critical health challenge, particularly in cases progressing to sepsis and septic shock, where host immune responses become dysregulated or dysfunctional. This study aims to evaluate the immunomodulatory effects of LHQK in severe pneumonia.

This research examined LHQK's therapeutic and immunomodulatory mechanisms in patients with severe pneumonia and a lipopolysaccharide (LPS)-induced mouse model of severe pneumonia. Patients with severe pneumonia were randomized into three groups: basal treatment, LHQK-Low dose (12 tablets/day), and LHQK-High dose (24 tablets/day). BALB/c mice were categorized into four groups: control, model, LHQK-Low dose (3.7 mg/kg), and LHQK-High dose (7.4 mg/kg). Clinical efficacy was evaluated by assessing parameters including the value and rate of change in APACHE II score, improvement in chest X-ray or CT, partial pressure of oxygen (PO₂), oxygen saturation in arterial blood (SaO₂), oxygenation index (OI), and the length of hospitalization after 7 days of treatment. The viscosity of sputum was measured by viscosimeter. Moreover, lung histopathology, airway barrier integrity, and immune cells in BALF, were assessed using hematoxylin and eosin staining, immunostaining, and Wright-Giemsa staining. Cytokine levels were measured using Luminex assay and Olink, while pulmonary immune cell patterns were analyzed using multiplex fluorescence and Cytometry by Time-Of-Flight (CyTOF).

In comparison to the basal treatment group of patients, LHQK treatment exhibited a reduction in the severity of severe pneumonia and inflammatory status, as evidenced by observations on Chest X-ray or CT scans. Additionally, LHQK treatment led to an elevation in OI, PO₂, and SaO₂ levels, and notably, a decreased duration of hospitalization. Further analysis revealed that LHQK enhanced the integrity of the airway epithelial barrier, reduced the viscosity of sputum, and significantly decreased inflammatory cells infiltration. The application of Luminex and Olink assay further confirmed the inhibitory impact of LHQK on the cytokine storm in mice. Moreover, multiplex fluorescence and CyTOF analysis demonstrated that LHQK effectively suppressed the activation of monocyte derived macrophages, neutrophils, and Treg cells, while preserved the levels of alveolar macrophages, B cells, and CD4⁺ and CD8⁺ T lymphocytes, therefore restoring immune homeostasis within the lung of severe pneumonia. These findings significantly substantiate the potential clinical application of LHQK in severe pneumonia treatment.

LHQK demonstrates therapeutic efficacy in severe pneumonia by maintaining structural integrity, suppressing cytokine storms, enhancing intrinsic immunity, reversing T cell exhaustion, and correcting lung immune disorders. These findings significantly substantiate LHQK's potential clinical application in severe pneumonia treatment.