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

作者全名："Wei, Qiang; Chen, Xi; Chen, Xia; Yuan, Zhongzhen; Wang, Chuanjiang"

作者地址："[Wei, Qiang; Chen, Xi] Chongqing Med Univ, Affiliated Hosp 1, Dept Lab Med, Chongqing, Peoples R China; [Chen, Xia] Army Med Ctr PLA, Dept Hlth Management, Chongqing, Peoples R China; [Yuan, Zhongzhen] Chongqing Univ, Canc Hosp, Dept Pharm, Chongqing, Peoples R China; [Yuan, Zhongzhen] Chongqing Canc Inst, Chongqing, Peoples R China; [Yuan, Zhongzhen] Chongqing Canc Hosp, Chongqing, Peoples R China; [Wang, Chuanjiang] Chongqing Med Univ, Affiliated Hosp 1, Dept Crit Care Med, Chongqing, Peoples R China"

通信作者："Wang, CJ (通讯作者)，Chongqing Med Univ, Chongqing, Peoples R China."

来源：SHOCK

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000797093700013

JCR分区：Q1

影响因子：3.1

年份：2022

卷号：57

期号：5

开始页：703

结束页：713

文献类型：Article

关键词：Apoptosis; cytokines; IL-38; P; aeruginosa pneumonia; Tregs

摘要："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-1 beta, IL-6, IL-17A, TNF-alpha, 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-1 beta, IL-6, IL-8, IL-17, TNF-alpha, 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-1 beta, IL-6, IL- 17A, TNF-alpha, 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."

基金机构："National Natural Science Foundation grants of China [81803110]; Basic science and cutting-edge technology research projects of Chongqing Science & Technology Commission [cstc2020jcyjmsxmX0014]; Medical Research Project of Chongqing City Health and Family Planning Committee [2020FYYX055, 2021MSXM010]"

基金资助正文："This study was supported by National Natural Science Foundation grants of China (81803110, to QW), Basic science and cutting-edge technology research projects of Chongqing Science & Technology Commission (cstc2020jcyjmsxmX0014, to CJ-W) and the Medical Research Project of Chongqing City Health and Family Planning Committee (2020FYYX055, to CJ-W, 2021MSXM010, to ZZ-Y)."