Lymphatic Flow: A Potential Target in Sepsis-Associated Acute Lung Injury

Abstract

Sepsis is life-threatening organ dysfunction caused by an imbalance in the body's response to infection and acute lung injury (ALI) related to sepsis is a common complication. The rapid morbidity and high mortality associated with sepsis is a significant clinical problem facing critical care medicine. Inflammation plays a vital role in the occurrence of sepsis. Notably, the body produces different immune cells and pro-inflammatory factors to clear pathogens. However, excessive inflammation can damage multiple tissues and organs when it fails to resolve in time. Additionally, lymphatic vessels could effectively transfer inflammatory cells and factors away from tissues and into blood circulation, thereby reducing damage, and promoting the resolution of inflammation. Therefore, any dysfunction and/or destruction of the lymphatic system may result in lymphedema followed by inflammatory storms and eventual sepsis. Consequently, the present study aimed to review and highlight the role of lymphatic vessels in related body tissues and organs during sepsis and other associated diseases.

Keywords: acute lung injury; lymphatic flow; sepsis.

Figure 1

A series of immune and inflammatory reactions are triggered after the body is invaded by foreign pathogens. After infection or injury, the invading pathogen encounters the host innate immune system. The innate cells “sense” pathogens by recognizing PAMP and DAMP through the amount of PRRS, including TLR, NLR and CLR. The NF-ΚB pathway is then activated and this transports pro-inflammatory factors through the lymphatic vessels to the site of inflammation. During sepsis, endothelial homeostasis is impaired in both blood and lymphatic vessels. In addition, the endothelial barrier is destroyed and permeability is increased.

Figure 2

How to remove the edema fluid and inflammatory cells in the alveoli during sepsis. Compared to the normal lung, a large amount of pulmonary edema fluid and inflammatory cells (B cell, Neutrophils, Macrophages) accumulate in the alveoli of the sepsis lung. They are mainly discharged through ENaC and Na⁺/K⁺ ATPase into the interstitial space and blood circulation. However, increasing evidence has shown that lymphatic vessels play a vital role in draining alveolar fluid and inflammatory cells. During sepsis, destruction of the structure of lymphatic vessels leads to flow dysfunction, causing pulmonary edema and disorder in the resolution of inflammation.