Contribution of IL-38 in Lung Immunity during Pseudomonas Aeruginosa-induced Pneumonia

Abstract

Objective:Interleukin-38 (IL-38), a new type of cytokine, is involved in processes such as tissue repair, inflammatory response, and immune response. However, its function in pneumonia caused by Pseudomonas aeruginosa (P. aeruginosa) is still unclear.Methods:In this study, we detected circulating IL-38 and cytokines such as IL-1β, IL-6, IL-17A, TNF-α, IL-8, and IL-10 in adults affected by early stage pneumonia caused by P. aeruginosa. Collected clinical data of these patients, such as the APACHE II score, levels of PCT, and oxygenation index when they entering the ICU. Using P. aeruginosa-induced pneumonia WT murine model to evaluate the effect of IL-38 on Treg differentiation, cell apoptosis, survival, tissue damage, inflammation, and bacterial removal.Results:In clinical research, although IL-38 is significantly increased during the early stages of clinical P. aeruginosa pneumonia, the concentration of IL-38 in the serum of patients who died with P. aeruginosa pneumonia was relatively lower than that of surviving patients. It reveals IL-38 may insufficiently secreted in patients who died with P. aeruginosa pneumonia. Besides, the serum IL-38 level of patients with P. aeruginosa pneumonia on the day of admission to the ICU showed significantly positive correlations with IL-10 and the PaO2/FiO2 ratio but negative correlations with IL-1β, IL-6, IL-8, IL-17, TNF-α, APACHE II score, and PCT In summary, IL-38 might be a molecule for adjuvant therapy in P. aeruginosa pneumonia. In experimental animal models, first recombinant IL-38 improved survival, whereas anti-IL-38 antibody reduced survival in the experimental pneumonia murine model. Secondly, IL-38 exposure reduced the inflammatory response, as suggested by the lung injury, and reduced cytokine levels (IL-1β, IL-6, IL- 17A, TNF-α, and IL-8, but not IL-10). It also increased bacterial clearance and reduced cell apoptosis in the lungs. Furthermore, IL-38 was shown to reduce TBK1 expression in vitro when naive CD4+ T lymphocytes were differentiated to Tregs and played a protective role in P. aeruginosa pneumonia.Conclusions:To summarize, the above findings provide additional insights into the mechanism of IL-38 in the treatment of P. aeruginosa pneumonia.

Emerging functions and therapeutic targets of IL‐38 in central nervous system diseases

“…IL-38 is a newly discovered cytokine in the IL-1 family and plays an important role in a variety of diseases, including but not limited to CNS diseases. [16][17][18][19][20][21][22][23][24] IL-38 is mainly expressed in the brain, heart, lungs, spleen, thymus, tonsils, and skin, and is less distributed in immune-inactive tissues. 25,26 Moreover, its protein is mainly synthesized and secreted by fibroblast-like synoviocytes, keratinocytes, peripheral blood mononuclear cells, and CD19+ B cells.…”

“…IL‐38 is a newly discovered cytokine in the IL‐1 family and plays an important role in a variety of diseases, including but not limited to CNS diseases 16–24 . IL‐38 is mainly expressed in the brain, heart, lungs, spleen, thymus, tonsils, and skin, and is less distributed in immune‐inactive tissues 25,26 .…”

Changes and Clinical Value of Serum miR-24 and miR-223 Levels in Patients with Severe Pneumonia

“…Nevertheless, with more involved contents, strong subjectivity, and low evaluation efficiency, it cannot provide effective reference for doctors to grasp the optimal treatment opportunity. 3,4 In recent years, studies have shown that microRNA (miRNA) and other biological indexes are closely related to the occurrence and development of pneumonia, which can offer reliable information for pneumonia diagnosis and treatment. [5][6][7] MiR-24 is a miRNA associated with inflammation, lung injury, and pneumonia progression.…”