Blockade of Interleukin‐17 Restrains the Development of Acute Lung Injury

Abstract

The acute respiratory distress syndrome (ARDS), a clinical complication of severe acute lung injury (ALI) in humans, is a leading cause of morbidity and mortality in critically ill patients. Here, we explored the association between IL-17 and development of ALI using LPS-induced murine model. We found that IL-17 level was elevated in bronchoalveolar lavage (BAL) fluid of ALI mice. Upregulation of IL-17 resulted in increased severity of ALI as evidenced by decreased body weight and survival rate, elevated level of total protein and albumin in BAL fluid, as well as more apparent histopathology changes of lung. Induction of ALI was impaired in IL-17-deficient mice. Management of IL-17 could modulate LPS-induced pulmonary inflammation, as reflected by the total cell and neutrophil counts, proinflammatory cytokines, as well as chemokines in BAL fluid. Of note, blockade of IL-17 effectively inhibited the lung inflammation and alleviated ALI severity. Finally, we confirmed the clinical relevance and found that IL-17 expression was elevated and associated with the disease severity in patients with ARDS. In essence, IL-17 was crucial for development of ALI, suggesting a potential application for IL-17-based therapy in clinical practice.

Pulmonary toxicity and inflammatory response of e-cigarettes containing medium-chain triglyceride oil and vitamin E acetate: Implications in the pathogenesis of EVALI but independent of SARS-COV-2 COVID-19 related proteins

“…IL-17 plays an important role in leukocyte infiltration. Studies have shown reduced G-CSF secretion in IL-17R-/- mice and that these mice were protected against ARDS [42,43]. In this study, aerosol exposure resulted in attenuated levels of MCP-1, RANTES, IL-17A, IL12p40, and IL-4 in BALF (Figure 6D-H).…”

COVID-19: a case for inhibiting IL-17?

“…Here, we argue that targeting IL-17 is immunologically plausible as a strategy to prevent acute respiratory distress syndrome (ARDS) in coronavirus disease 2019 (COVID-19) and discuss why we think that a clinical trial of a drug in this class could be a logical addition to the effort to find effective therapies. study, mice genetically deficient in IL-17 or those that received anti-IL-17 antibodies demonstrated improved survival, less lung infiltration and better lung pathology scores following LPS challenge 8 .…”

From sepsis to acute respiratory distress syndrome (ARDS): emerging preventive strategies based on molecular and genetic researches

“…The release of many cytokine and the regulation of inflammatory pathways are regulated by some transcription factors such as NF-κB, thus, any changes in their structure and expression might influence cytokine production and ARDS progress [61]. Since increased IL-17 may serve as a biomarker to indicate the severity of ARDS in patients with sepsis-induced ARDS [62], researchers have estimated the IL-17 (rs763780, rs2275913, and rs8193036) and NF-κB1 (rs3774934) polymorphisms in a Chinese population that were associated with ARDS prediction and prognosis [63]. This conclusion further shows that the detection of related gene expression and variants has an important role in the prediction and prevention of the occurrence and development of ARDS.…”