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 is still unclear.Methods: In this study, we detected circulating IL-38 in adults affected by pneumonia caused by P. aeruginosa. The P. aeruginosa-induced pneumonia WT murine model was adopted to evaluate the effect of IL-38 on Treg differentiation, cell apoptosis, survival, tissue damage, inflammation, and bacterial removal.Results: IL-38 is insufficiently secreted in patients who died of P.A. pneumonia.Recombinant IL-38 improved survival, whereas anti-IL-38 antibody reduced survival in the experimental pneumonia murine model. 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 CXCL-1, 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 naïve CD4+ T lymphocytes were differentiated to Tregs and played a protective role in P.A. pneumonia.Conclusions: To summarize, the above findings provide additional insights into the mechanism of IL-38 in the treatment of P.A. pneumonia.

Immunobiological Properties and Clinical Applications of Interleukin-38 for Immune-Mediated Disorders: A Systematic Review Study

“…As reviewed in this study, alterations in serum levels of IL-38 played a major role in the immunopathogenesis of many diseases, in which patients had been previously faced with a wide array of problems due to the lack of prognosis or accurate diagnosis and improper treatment [213][214][215][216][217][218][219][220][221]. At the time of the literature review for this systematic review study, as there is a global pandemic of Coronavirus, it has been demonstrated that anti-inflammatory properties of IL-38 can be considered as recently-emerged pharmacotherapies for alleviation of the inflammatory symptoms of patients with SARS-CoV-2 infection [186,222].…”