Fang Xu1, Shihui Lin1, Xingxing Yan2, Chuanjiang Wang1, Hongmei Tu2, Yibing Yin3, Ju Cao2. 1. Department of Emergency and Intensive Care Unit, China. 2. Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, China. 3. Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, China.
Abstract
Background: Interleukin 38 (IL-38) is the most recently characterized cytokine of the interleukin 1 family. However, its role in sepsis remains unknown. Methods: Circulating IL-38 levels were measured in 2 cohorts of adult and pediatric patients with sepsis. Using 2 murine models of lipopolysaccharide (LPS)-induced endotoxemia and cecal ligation and puncture (CLP)-induced sepsis, the effects of IL-38 on survival, inflammation, tissue injury, and bacterial clearance were assessed. Results: Serum IL-38 concentrations were significantly elevated in adult and pediatric patients with sepsis relative to corresponding healthy adult and pediatric controls, respectively. An increased IL-38 level negatively correlated with the number of blood leukocytes and with the level of inflammatory cytokines, including interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in clinical sepsis. Anti-IL-38 antibody impaired survival and while recombinant IL-38 improved survival in the 2 murine models of LPS-induced endotoxemia and CLP-induced sepsis. IL-38 administration decreased the inflammatory response, as reflected by lower levels of cytokines and chemokines (including IL-6, TNF-α, interleukin 10, interleukin 17, interleukin 27, CXCL1, and CCL2), and less damage to tissues (including lung, liver, and kidney) in CLP-induced sepsis. Furthermore, IL-38 augmented bacterial clearance in CLP-induced polymicrobial sepsis. Conclusions: These findings suggest that IL-38 attenuates sepsis by decreasing inflammation and increasing bacterial clearance, thus providing a novel tool for antisepsis therapy.
Background: Interleukin 38 (IL-38) is the most recently characterized cytokine of the interleukin 1 family. However, its role in sepsis remains unknown. Methods: Circulating IL-38 levels were measured in 2 cohorts of adult and pediatric patients with sepsis. Using 2 murine models of lipopolysaccharide (LPS)-induced endotoxemia and cecal ligation and puncture (CLP)-induced sepsis, the effects of IL-38 on survival, inflammation, tissue injury, and bacterial clearance were assessed. Results: Serum IL-38 concentrations were significantly elevated in adult and pediatric patients with sepsis relative to corresponding healthy adult and pediatric controls, respectively. An increased IL-38 level negatively correlated with the number of blood leukocytes and with the level of inflammatory cytokines, including interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in clinical sepsis. Anti-IL-38 antibody impaired survival and while recombinant IL-38 improved survival in the 2 murine models of LPS-induced endotoxemia and CLP-induced sepsis. IL-38 administration decreased the inflammatory response, as reflected by lower levels of cytokines and chemokines (including IL-6, TNF-α, interleukin 10, interleukin 17, interleukin 27, CXCL1, and CCL2), and less damage to tissues (including lung, liver, and kidney) in CLP-induced sepsis. Furthermore, IL-38 augmented bacterial clearance in CLP-induced polymicrobial sepsis. Conclusions: These findings suggest that IL-38 attenuates sepsis by decreasing inflammation and increasing bacterial clearance, thus providing a novel tool for antisepsis therapy.
Authors: Xun Gao; Paul Kay Sheung Chan; Grace Chung Yan Lui; David Shu Cheong Hui; Ida Miu-Ting Chu; Xiaoyu Sun; Miranda Sin-Man Tsang; Ben Chung Lap Chan; Christopher Wai-Kei Lam; Chun-Kwok Wong Journal: Cell Death Dis Date: 2021-01-07 Impact factor: 8.469
Authors: Dennis M de Graaf; Ralph J A Maas; Sanne P Smeekens; Elan Eisenmesser; Jasmina S Redzic; Monique M Helsen; Nicholas E Powers; Suzhao Li; Vassili Kalabokis; Mark S Gresnigt; Leo A B Joosten; Charles A Dinarello; Frank L van de Veerdonk Journal: Cytokine Date: 2020-10-28 Impact factor: 3.861