Photodynamic Therapy of LD4-Photosensitizer Attenuates the Acute Pneumonia Induced by Klebsiella pneumoniae

ACS Pharmacol Transl Sci. 2024 Mar 5;7(4):1101-1113. doi: 10.1021/acsptsci.3c00392. eCollection 2024 Apr 12.

Abstract

Klebsiella pneumoniae is a Gram-negative bacterium that induces acute lung injury (ALI) and inflammation in humans, necessitating immediate hospitalization and treatment. At present, the clinical treatment is largely dependent on hormones or antibiotics but is associated with drawbacks posed by the lack of eradication of the bacterium upon treatment and drug resistance. Therefore, there is an urgent need for novel and effective treatments. The current study investigated the treatment of K. pneumonia-induced ALI using a photosensitizer LD4 in conjunction with photodynamic therapy (PDT). The water content in the lungs (corresponding to edema) of a rat model of pneumonia induced by K. pneumoniae was reduced upon treatment with LD4-PDT. The counts of leukocyte, lymphocyte, and polymorphonuclear leukocyte in the blood were determined in the rat model of pneumonia, as were the concentrations of inflammatory cytokines (estimated using an enzyme-linked immunosorbent assay). The LD4-PDT treatment prominently reduced the levels of interleukin (IL)-6, IL-10, tumor necrosis factor-α, superoxide dismutase, and immune cells. Results suggest that LD4-PDT considerably alleviates the inflammation and oxidative stress caused by K. pneumoniae in the rat model of pneumonia. Furthermore, it could effectively improve the survival rate in the rat model of K. pneumonia-induced pneumonia and ameliorate histological changes while protecting the integrity of the pulmonary epithelial cells. These results highlight the potential application of LD4 as a photosensitizer for treating acute pneumonia induced by K. pneumoniae.