title: CD16 inhibition increases host survival in a murine model of severe sepsis.
abstract: BACKGROUND
  To investigate the therapeutic effect of monoclonal antibody (mAb)-induced CD16 (FcγRIII) inhibition in a murine model of high-grade (severe) sepsis.
  
  
  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: Department of Emergency and Critical Care Medicine, Changhai Hospital, Shanghai, China.
authors: Dewen
authors: D
authors: Zhang
authors: Department of Emergency and Critical Care Medicine, Changhai Hospital, Shanghai, China. Electronic address: hejiansmmu@126.com.
authors: Jian
authors: J
authors: He
authors: Department of Emergency and Critical Care Medicine, Changhai Hospital, Shanghai, China.
authors: Meihua
authors: M
authors: Shen
authors: Department of Emergency and Critical Care Medicine, Changhai Hospital, Shanghai, China.
authors: Rui
authors: R
authors: Wang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002432:Cecum / Q000293:injuries; D004195:Disease Models, Animal; D007274:Injections, Intraperitoneal; D053208:Kaplan-Meier Estimate; D008026:Ligation; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D010538:Peritonitis / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D017452:Receptors, IgG / Q000037:antagonists & inhibitors* / Q000276:immunology; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000911:Antibodies, Monoclonal; C485700:Fcgr3 protein, mouse; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha
keywords: Animal model; CD16/32 monoclonal antibody; Cytokine; Flow cytometry; High-grade sepsis; IL-1β; Monocyte; TNF-α