Dewen Zhang1, Jian He2, Meihua Shen1, Rui Wang1. 1. Department of Emergency and Critical Care Medicine, Changhai Hospital, Shanghai, China. 2. Department of Emergency and Critical Care Medicine, Changhai Hospital, Shanghai, China. Electronic address: hejiansmmu@126.com.
Abstract
BACKGROUND: To investigate the therapeutic effect of monoclonal antibody (mAb)-induced CD16 (FcγRIII) inhibition in a murine model of high-grade (severe) sepsis. MATERIALS AND METHODS: In a prospective controlled animal study, 2 μg of CD16/32 (FcγRIII/FcγRII) or the same volume of normal saline was administered intraperitoneally to BALB/c FcγRII(-/-) mice at the time of cecal ligation and puncture (CLP) in a murine model of high-grade sepsis. Subcutaneous administration of CD16/32 (0.5 μg/24 h) or normal saline continued for 7 d. Survival was evaluated, and the underlying therapeutic mechanism of mAb-induced CD16 inhibition was investigated. RESULTS: CD16 expression was significantly increased on peripheral blood CD14(+) monocytes from mice with high-grade sepsis compared with non-septic control mice (1579.40 ± 217.75 versus 461.10 ± 36.13; P < 0.05). CD16/32 mAb treatment increased the survival of mice with high-grade sepsis (P < 0.05) and significantly decreased their elevated levels of serum tumor necrosis factor α (36.70 ± 9.97 versus 52.60 ± 10.69; P < 0.05) and interleukin 1β (1149.40 ± 244.09 versus 2605.60 ± 353.74; P < 0.05) at 6 and 24 h after CLP, respectively. Moreover, CD16/32 mAb-treated mice with high-grade sepsis had fewer bacteria in their blood and peritoneal lavage than mice just treated with normal saline at 24 h after CLP (P < 0.05). CONCLUSIONS: CD16/32 mAb-induced CD16 inhibition increased the survival of mice with high-grade sepsis, which may have been because of the concomitant suppression of tumor necrosis factor α and interleukin 1β as well as the enhancement of monocyte phagocytosis. Thus, targeted inhibition of CD16 can potentially improve the outcome of selected patients with severe sepsis.
BACKGROUND: To investigate the therapeutic effect of monoclonal antibody (mAb)-induced CD16 (FcγRIII) inhibition in a murine model of high-grade (severe) sepsis. MATERIALS AND METHODS: In a prospective controlled animal study, 2 μg of CD16/32 (FcγRIII/FcγRII) or the same volume of normal saline was administered intraperitoneally to BALB/c FcγRII(-/-) mice at the time of cecal ligation and puncture (CLP) in a murine model of high-grade sepsis. Subcutaneous administration of CD16/32 (0.5 μg/24 h) or normal saline continued for 7 d. Survival was evaluated, and the underlying therapeutic mechanism of mAb-induced CD16 inhibition was investigated. RESULTS:CD16 expression was significantly increased on peripheral blood CD14(+) monocytes from mice with high-grade sepsis compared with non-septic control mice (1579.40 ± 217.75 versus 461.10 ± 36.13; P < 0.05). CD16/32 mAb treatment increased the survival of mice with high-grade sepsis (P < 0.05) and significantly decreased their elevated levels of serum tumor necrosis factor α (36.70 ± 9.97 versus 52.60 ± 10.69; P < 0.05) and interleukin 1β (1149.40 ± 244.09 versus 2605.60 ± 353.74; P < 0.05) at 6 and 24 h after CLP, respectively. Moreover, CD16/32 mAb-treated mice with high-grade sepsis had fewer bacteria in their blood and peritoneal lavage than mice just treated with normal saline at 24 h after CLP (P < 0.05). CONCLUSIONS:CD16/32 mAb-induced CD16 inhibition increased the survival of mice with high-grade sepsis, which may have been because of the concomitant suppression of tumor necrosis factor α and interleukin 1β as well as the enhancement of monocyte phagocytosis. Thus, targeted inhibition of CD16 can potentially improve the outcome of selected patients with severe sepsis.
Authors: Per Flodbring Larsson; Richard Karlsson; Martuza Sarwar; Regina Miftakhova; Tianyan Wang; Azharuddin Sajid Syed Khaja; Julius Semenas; Sa Chen; Andreas Hedblom; Amjad Ali; Kristina Ekström-Holka; Athanasios Simoulis; Anjani Kumar; Anette Gjörloff Wingren; Brian Robinson; Sun Nyunt Wai; Nigel P Mongan; David M Heery; Daniel Öhlund; Thomas Grundström; Niels Ødum; Jenny L Persson Journal: Mol Oncol Date: 2022-01-23 Impact factor: 7.449