CD16 inhibition increases host survival in a murine model of 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.